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“Benign and Malignant Epithelial Oral ” Edward Halusic, Jr., DMD

Benign and Malignant Epithelial Oral Pathology

Edward J. Halusic, DMD Diplomate, American Board of Oral and Maxillofacial Surgery Private Practice, Greensburg, Pa.

POMA District VIII 32nd Annual Educational Winter Seminar Sunday, February 3, 2019 Nemacolin Woodlands

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Disclosures

None

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Course Objectives

Upon Completion of the course, participants will be familiar with:

Differential diagnosis of some common reactive processes and soft tissue lesions in the oral cavity

Management strategies for these lesions

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POMA District VIII 32nd Annual Educational Winter Seminar January 31-February 3, 2019 1 “Benign and Malignant Epithelial Oral Pathology” Edward Halusic, Jr., DMD

Outline

Epithelial Pathology

Normal anatomic variants

Inflammatory

Infectious

Reactive/Traumatic

Premalignant

Malignant

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Geographic Benign Migratory Migrans

• Harmless Condition

• Well defined, reddened areas on the dorsal and lateral tongue with slightly white or yellow-white, raised lines around the edges

• Condition usually waxes ad wanes in severity persisting for a period of time (days to weeks to months)

• Process repeats itself in a different area or areas after a few more days, weeks or months

• When the condition is “active”, the tongue is often sensitive and can feel like it has been scalded to hot, spicy, or acidic foods.

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Burning Mouth Syndrome

• Chronic Pain Condition • Intraoral burning recurring for more than 2 hours per day for more than 3 months without clinically evident causative lesions • Women 7:1. • Usually perimenopausal or menopausal age group. • 0.7 to 15 % of the population • Anterior two thirds of the tongue • Taste alterations • Oral Dryness

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POMA District VIII 32nd Annual Educational Winter Seminar January 31-February 3, 2019 2 “Benign and Malignant Epithelial Oral Pathology” Edward Halusic, Jr., DMD

Burning Mouth Syndrome

• Complex disease without a clear etiology • Not well understood or well managed by medicine or dentistry • Neuropathic. • Gustatory • Primary BMS: No local or systemic causes can be identified • Secondary BMS: Local or systemic caused can be identified • Prognosis is poor. Spontaneous remission in only about 3% of patients in 5 years.

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Burning Mouth Syndrome Symptoms

• Burning of • Alteration in taste such as bitter or metallic tastes • Oral Dryness (Xerostomia) in spite of normal salivary flow • Roughness, sandiness texture • All of these symptoms can significantly affect quality of life

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Burning Mouth Syndrome Diagnosis Must rule out Secondary BMS

Fungal Infections Mechanical Trauma Thermal Trauma Chemical Injury Xerostomia Parafunctional Habits Oral Pathology Allergic Contact

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POMA District VIII 32nd Annual Educational Winter Seminar January 31-February 3, 2019 3 “Benign and Malignant Epithelial Oral Pathology” Edward Halusic, Jr., DMD

Burning Mouth Syndrome Diagnosis Substance List for Allergic Chemicals Where found Zinc, Cobalt, Mercury, Gold, Palladium Dental Materials Nickel Sulfate Dental Materials, Stainless Steel, Food (e.g., shrimp and chocolate milk) Sodium Lauryl Sulfate Toothpaste Fragrance Mix Oral Care Products Balsam of Peru Oral Care Products, Citrus Fruits, Spices, Cough Medicines and Lozenges Cinnamic Alcohol Cinnamon and products with cinnamon flavor Nasri-Heir et al, J Indian Prosthodontic Society, 2015 Oct-Dec; 15)4): 300-307 #POMAD8 #ChoosePOMA 11

Burning Mouth Syndrome Diagnosis Must rule out Secondary BMS

Endocrine Disorders Immunological Disorders (Sjogren’s) GERD

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Burning Mouth Syndrome Diagnosis Must rule out Secondary BMS

Basic Metabolic Panel Iron Serum levels/ferritin Vitamin B12 and folate levels to rule out associated ANA, Anti/SS-A, Anti/SS-B, Rheumatoid Factor to rule out Sjogren’s CBC Cytological smears if candidiasis is suspected Salivary Flow Rates if xerostomia is suspected Skin Patch Tests if allergic reactions are suspected #POMAD8 #ChoosePOMA 13

POMA District VIII 32nd Annual Educational Winter Seminar January 31-February 3, 2019 4 “Benign and Malignant Epithelial Oral Pathology” Edward Halusic, Jr., DMD

Burning Mouth Syndrome Diagnosis Must rule out Secondary BMS

Medications (Augment/Induce Burning(ACE), Xerostomia)

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Medications related to Hyposalivation/Xerostomia

Medications Examples Tricyclic Antidepressants Amitriptyline, nortriptyline Antipsychotic Carbidopa/levodopa,chlorpromazine Antihistaminic Phenergan Bronchodilator (anticholinergic and B-2 Tiotropium, formoterol agonist) Decongestant Oxymetazoline Antidepressant Venlafaxine Skeletal muscle relaxant Tizanidine Antihypertensives Furosemide, clonidine, lisinopril, verapamil Chemotherapy Cyclophosamide Protease inhibitor for HIV Reyataz, Norvir, Kaletra Opioid Hydrocodone, oxycodone Benzodiazepine Diazepam

#POMAD8 Nasri-Heir et al, J Indian Prosthodontic Society, 2015 Oct-Dec; 15)4): 300-307 #ChoosePOMA 15

Treatment of Burning Mouth Syndrome

Benzodiazepenes:

• Clonazepam. GABA agonist.

• 70% reduction in pain levels with oral dose of 0.5-1.5 mg/day to maximum of 3 mg. (Grushka et al.)

• Significant reduction in pain at dose of 0.5 mg/day after 9 weeks of treatment when compared to control group. (Heckman et al.)

Nasri-Heir et al, J Indian Prosthodontic Society, 2015 Oct-Dec; 15)4): 300-307

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POMA District VIII 32nd Annual Educational Winter Seminar January 31-February 3, 2019 5 “Benign and Malignant Epithelial Oral Pathology” Edward Halusic, Jr., DMD

Treatment of Burning Mouth Syndrome

Anticonvulsants such as gabapentin at 300 mg/day showed some favorable results in one study which could not be confirmed in another study.

Tricyclic antidepressants at 10-40 mg/day have shown to be beneficial in relieving pain although side effect of xerostomia may be unfavorable.

SSRI’s: Paroxetine with initial dose of 10-20 mg/day to maximum of 30 mg/day revealed 80% of patients experienced pain reduction with 12 weeks.

Serotonin noradrenaline reuptake inhibitors: significant decrease in pain levels after 12 weeks of treatment with minalcipran 15 mg/day to 100 mg/day.

Histamine H2 receptor antagonist: significant improvement in pain levels using lafutidine(India) 10 mg twice daily for 12 weeks. It has a sensitive effect on capsaicin- sensitive afferent neurons improvement in pain levels using lafutidine 10 mg twice daily for 12 weeks. In US, equivalent would be famotidine or ranitidine.

#POMAD8 Nasri-Heir et al, J Indian Prosthodontic Society, 2015 Oct-Dec; 15)4): 300-307 #ChoosePOMA 17

Treatment of Burning Mouth Syndrome

Alpha Lipoic Acid: Potent antioxidant. One study showed efficacy while another did not confirm the results.

Topical: Capsaicin. Hot component of chili peppers.

Topical Treatment: Clonazepam. 1.0 mg dissolved. 3 times per day. Hold for 3 minutes and expectorate. 66% of patients reported resolution of symptoms and 29% reported partial reduction of symptoms after 6 months.

Psychologic/Psychiatric Intervention: Individual or small group cognitive-behavior therapy has been shown to reduce the intensity of the pain of BMS. Some authors feel this is a critical component of treating patients with BMS as 50% of patients presented with psychiatric disorders including anxiety, depression, obsessive or psychosomatic symptoms.

#POMAD8 Nasri-Heir et al, J Indian Prosthodontic Society, 2015 Oct-Dec; 15)4): 300-307 #ChoosePOMA 18

Treatment of Burning Mouth Syndrome

• Foods that cause burning or exacerbate symptoms should be avoided. ( Pineapple, tomato orange, lemon,etc.)

• Smoking, alcohol, and mouth rinses with alcohol should be avoided

• Toothpastes with abrasive substances should be avoided.

#POMAD8 Nasri-Heir et al, J Indian Prosthodontic Society, 2015 Oct-Dec; 15)4): 300-307 #ChoosePOMA 19

POMA District VIII 32nd Annual Educational Winter Seminar January 31-February 3, 2019 6 “Benign and Malignant Epithelial Oral Pathology” Edward Halusic, Jr., DMD

Common chronic mucocutaneous autoimmune mediated disease – 1.27% prevalence

• Most common in women 30‐60 yrs – 3:2 to female to male

• Associated with cell‐mediated immunologic dysfunction Erosive

Skin Lesions • 4P’s Reticular - Purple - Pruritic - Polygonal - Papules

- Most commonly seen on the flexor surfaces #POMAD8 #ChoosePOMA 20

Topical Steroids Lichen Planus Treatment Systemic Steroids Systemic Steroid Sparing Agents (Calcineurin Inhibitors) -Tacrolimnus (topical) -Cyclosporine (topical)

Erosive

Skin Lesions • 4P’s Reticular - Purple - Pruritic - Polygonal - Papules

- Most commonly seen on the flexor surfaces #POMAD8 #ChoosePOMA 21

Lichen Planus Treatment

Topical Steroids

Dexamethasone Elixir (.5mg/ml) Lidex Gel (Fluocinonide) 0.05% • Disp: 30 g tube • Disp: 250cc • Coat the lesion with a thin film after • Sig: Rinse with 1 teaspoon (5ml) 4 each meal and at bedtime times a day and spit

• Do not eat or drink for 30 minutes after using the elixir • Advantages- covers large area of oral * Can be compounded with Orabase cavity (methylcellulose base) #POMAD8 #ChoosePOMA 22

POMA District VIII 32nd Annual Educational Winter Seminar January 31-February 3, 2019 7 “Benign and Malignant Epithelial Oral Pathology” Edward Halusic, Jr., DMD

Lichen Planus Treatment

Calcineurin Inhibitor

Tacrolimus 0.1% • Disp: 30 g tube • Sig: Apply to affected site twice daily

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Lichen Planus Treatment

Systemic Steroids

Medrol Dose Pack Prednisone • Disp: One pack • 8 week regimen. 10 mg. x 105 tablets. • Sig: Use as directed • 20 mg four times per day every other day for two weeks. • 20 mg twice per day every other day for two weeks. • 20 mg once per day every other day for two week. • 10 mg once per day every other day for two weeks.

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Complications of Steroid Therapy

• Susceptibility to infection -

• Insomnia - Dose oral steroids in the morning

• Hyperglycemia • Poor wound healing • Capillary fragility • Hypertension • Glaucoma • Adrenal suppression • Mood swings • Peptic ulceration - Care with ASA/NSAIDS, consider PPI

• Cushing syndrome #POMAD8 #ChoosePOMA 25

POMA District VIII 32nd Annual Educational Winter Seminar January 31-February 3, 2019 8 “Benign and Malignant Epithelial Oral Pathology” Edward Halusic, Jr., DMD

Squamous cell arising in Lichen Planus

• Reported 0.04 to 1.74% of oral lichen planus has malignant transformation to - Mainly erosive & atrophic forms, poorly controlled

• Must see classic LP i.e. bilateral, symmetric, reticulated, at the usual sites • Repeat if change in the character of the lesions

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Case

• 54 year old female presents with a 13 month history of “oral sores” Differential Diagnoses • She has seen numerous providers - Past diagnoses and treatment include: , thrush, and herpes • Lichenoid Drug Reaction • PMHx: Hx MI, Hx pericardial effusion, gout • Meds: Aspirin, Carvedilol, Citalopram, Furosemide, • Lichenoid Contact Stomatitis Docusate Sodium, Eliquis, Atorvastatin, Allopurinol, Albuterol, Maalox, Ambien, Magic Swizzle, Zofran (prn) • Chronic Ulcerative Stomatitis

• Vesiculobullous disease

Erythematosus

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Case

• 54 year old female presents with a 13 month history of “oral sores” • She has seen numerous providers Differential Diagnoses - Past diagnoses and treatment include: shingles, thrush, and herpes • Lichenoid Drug Reaction • PMHx: Hx MI, Hx pericardial effusion, gout • Meds: Aspirin, Carvedilol, Citalopram, Furosemide, • Lichenoid Contact Stomatitis Docusate Sodium, Eliquis, Atorvastatin, Allopurinol, Albuterol, Maalox, Ambien, Magic Swizzle, Zofran (prn) • Chronic Ulcerative Stomatitis

• Vesiculobullous disease allopurinol •

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POMA District VIII 32nd Annual Educational Winter Seminar January 31-February 3, 2019 9 “Benign and Malignant Epithelial Oral Pathology” Edward Halusic, Jr., DMD

Medications associated with lichenoid reactions Differential Diagnoses - Antihypertension agents • Lichenoid Drug Reaction - Diurectics (e.g. HCTZ), beta blockers, ACE inhibitors • Lichenoid Contact Stomatitis - Sulfonylureas - Levothyroxine • Chronic Ulcerative Stomatitis - Sulfasalazine - Allopurinol • Vesiculobullous disease - NSAIDs - Carbamazepine • Lupus Erythematosus - Some statins - Biologics such as TNF alpha inhibitor

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Lichenoid Reaction to Gold Differential Diagnoses

• Lichenoid Drug Reaction

• Lichenoid Contact Stomatitis

• Chronic Ulcerative Stomatitis

• Vesiculobullous disease

• Lupus Erythematosus

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New Case

• 66 yo female presents with CC of “my hurt bad” • PMHx: Hypertension, thyroid disease, and • She is being worked up for autoimmune disease • Arthritis vs connective tissue disorder associated with a rash on her chest and arms for years • Meds: Prednisone 5 mg/day, Citalopram, Bupropion, Lisonopril, Levothyroxine, Methotrexate, Folic Acid, and Vitamin C, B12 injections

Exam

• Posterior left lateral border of the tongue, there is a 1cm ulcer • Maxillary left alveolar crestal mucosa tooth area 13: There is erythema and a 0.3 cm small ulceration • Right mandibular alveolar crest, #30 area: ulcer with a pseudomembrane 0.5 to 0.7 cm

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POMA District VIII 32nd Annual Educational Winter Seminar January 31-February 3, 2019 10 “Benign and Malignant Epithelial Oral Pathology” Edward Halusic, Jr., DMD

Biopsy of tongue: Ulcer and Epithelial Dysplasia

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New Case

• 66 yo female presents with CC of “my gums hurt bad” Methotrexate • PmHx: Hypertension, thyroid disease, and arthritis • She is being worked up for autoimmune disease • Arthritis vs connective tissue disorder associated with a rash on her chest and arms for years • Meds: Prednisone 5 mg/day, Citalopram, Bupropion, Lisonopril, Levothyroxine, Methotrexate, Folic Acid, and Vitamin C, B12 injections

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Potential etiologies for oral ulceration

• Trauma • Mucocutaneous Disease • Factitious • Lichen planus • Chemical • • Idiopathic • Benign • Recurrent vulgaris • -Related Ulceration • Autoimmune/Systemic Diseases • Infectious Ulceration • Celiac disease • Viral • Crohn’s • virus • Bechet’s disease • Varicella zoster (Shingles) • Lupus erythematous • Epstein-Barr virus • Fungal

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POMA District VIII 32nd Annual Educational Winter Seminar January 31-February 3, 2019 11 “Benign and Malignant Epithelial Oral Pathology” Edward Halusic, Jr., DMD

Clinical History • Patient Presents with non-healing ulcer of several weeks duration

• CC: “My tongue hurts”

• History reveals patient was biting his tongue during the night and was waking up in pain. Post Occlusal Guard Ulcer seem to be secondary to repetitive trauma.

• Dx: Nocturnal Tongue Biting

• Rx: Occlusal Night Guard to protect tongue from trauma of biting.

Pre Occlusal Guard Pre Occlusal Guard

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Aphthous Ulcers

• 10-20% of the general population • 40+% of college-age pop during exams • Idiopathic • Immune dysregulation • Tan-gray surface coat with fiery red-halo • Origin on loose, NON-keratinized mucosa • Unlikely to develop AFTER ~40yrs

3 Forms

• Minor • 80%, 4-6mm diameter, round to oval, 7- 10 day duration • Major • More rare, >1 cm, irregular outline, 4-6 week duration, heals with scaring • Clusterform • Punctate 2-3 mm, 10-100 lesions, • Extend onto keratinized tissue #POMAD8 #ChoosePOMA 36

Treatment-Aphthous Ulcers

• Rx: Triamcinolone acetonide (Kenalog) in Orabase 0.1% Disp: 5gm tube Sig: Apply to affected area t.i.d. for no more than 2 weeks (DO NOT RUB IN) MBX for palliative treatment.

• Rx: Dexamethasone elixir (0.5mg/5ml) Equal part of: Disp:200cc - 2% Viscous Xylocaine Sig: Swish with 1 tsp for 2 min then spit out, q.i.d. - Maalox -Benadryl Elixir (2.5 mg/ml) Treatment is usually only for major or multiple, symptomatic aphthae.

Do no eat or brush 30 minutes after application.

#POMAD8 Clinician’s Guide Treatment of Common Oral Lesions. Siegel, Silverman, and Collection 6th Ed. BC Decker. #ChoosePOMA 37

POMA District VIII 32nd Annual Educational Winter Seminar January 31-February 3, 2019 12 “Benign and Malignant Epithelial Oral Pathology” Edward Halusic, Jr., DMD

• Aphthous stomatitis • Herpes stomatitis

• No vesicles • Mult. Small vesicles • Begins as an ulcer • Merge to form ulcers • Disproportionate pain • Painful • Loose, non-keratinized • Keratinized mucosa mucosa • Irrregular • Round, oval red halo

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Herpes Simplex Virus

• Retrograde travels to sensory ganglia • Virus remains dormant in ganglia until reactivation • Viral latency • Recurrence is heralded by itching, tingling, burning sensation • Virus then travels down sensory nerve • Reinfecting • Fragile vesicles form in clusters on keratinized epithelium • Scratching vesicles can lead to autoinoculation of other sites

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Treatment – Recurrent HSV

• Rx: Docansol (Abreva) cream (OTC) Disp: 2gm tube Dab on lesion 5 times daily during waking hours, for 4 days beginning when symptoms first appear. (NOT for use intraorally. On only.)

• Rx: Valacyclovir (Valtrex) caplets 500 mg Disp: 8 caps Take 4 caps as soon as prodromal symptoms are recognized and then 4 caps twelve hours later

• Lysine 1000 mg; 500 mg twice per day.

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POMA District VIII 32nd Annual Educational Winter Seminar January 31-February 3, 2019 13 “Benign and Malignant Epithelial Oral Pathology” Edward Halusic, Jr., DMD

Suggested Drug Therapies for Oral Candidiasis

Rx: Mycelex (clotrimazole) troches 10mg or Nystatin pastilles • Disp: 70 troches (or pastilles) • Sig: 1 troche (or pastille) dissolved slowly in mouth 5 times a day for 14 days

Rx: Fluconazole (Diflucan) tablets 100mg • Disp.: 15 tabs • Sig: Take 2 tabs stat, then 1 tablet daily until gone

Patients with denture stomatitis (with candidiasis) Rx: Nystatin ointment • Disp: 30 gram tube • Sig: Apply to denture base and insert denture t.i.d. (Note: The patient should also be instructed to clean denture and soak. If the patient wears a partial denture with metal connectors, avoid bleach solutions– Use OTC soaking product or Nystatin suspension)

#POMAD8 Clinician’s Guide Treatment of Common Oral Lesions . Siegel, Silverman, & Sollecito. 6th Ed. BC #ChoosePOMA 41

Squamous

• Caused by HPV 2, 6, 11, 57 (low risk types) • Immunosuppressed patients at a higher risk • Painless exophytic pedunculated or sessile masses with a cauliflower-like surface • Most frequent sites: soft , tongue, • Less than 0.5 cm in diameter • Differential: Verruca, condyloma, Heck’s • Treatment: Surgical excision

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• Patient presents with an exophytic white lesion lower lip Verruca Vulgaris (common ) • Previous excision in 2008 • HPV 2, 4, 6, 40 (low risk types) • Can spread by autoinoculation • Most common in children • Most frequent intraoral sites are lip, labial mucosa, and anterior tongue • Single or multiple, white, pedunculated or sessile, papillary or pebbly lesion(s)

Treatment • Excision • CO2 Laser: High rate of efficacy

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POMA District VIII 32nd Annual Educational Winter Seminar January 31-February 3, 2019 14 “Benign and Malignant Epithelial Oral Pathology” Edward Halusic, Jr., DMD

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Clinical History- 74 yo female

• Patient presents with a rough white patch of the maxillary molar area (#2-3) of 3 years duration. • A smaller patch is present on the contralateral side in the area of #13-14. • PMHx: Hypothyroidism, Hx rheumatic fever • SH: 1/2ppd (15 pack years) • Ddx: ,

Diagnosis

• Papillary • Mild epithelial dysplasia

• PVL? Proliferative Veruccous

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Case History

• 71 yo female • Greater than 1 year history of multiple tongue lesions. • “Fibrotic tissue at the lateral border of the tongue and papillary growths present adjacent to the fibrotic tissue.” • PMHx-hypertension, osteoporosis, hyperlipidemia and Sjogren’s syndrome. • Previous pathology report from the right buccal mucosa interpreted as a benign squamous papilloma from an outside institution.

Verrucous CA Papillary keratosis with dysplasia

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POMA District VIII 32nd Annual Educational Winter Seminar January 31-February 3, 2019 15 “Benign and Malignant Epithelial Oral Pathology” Edward Halusic, Jr., DMD

MAJOR CRITERIA MINOR CRITERIA Proliferative Verrucous Leukoplakia: A. A leukoplakic lesion with A. An oral leukoplakic lesion that more than two different oral sites. occupies at least 3 cfm when adding all • Condition characterized by the development B. The existence of a verrucous the affected areas. of multiple, persistent, leukoplakias area. B. The patient is a female. • Not associated with tobacco use C. The lesions have spread or C. The patient (male or female) is a non- enlarged during development smoker. • Many will develop a verrucous carcinoma of the disease. D. A disease evolution higher than 5 and/or a squamous cell carcinoma D. There has been a recurrence in years. • Long term follow-up warranted a previously-treated area. E. Histopathologically, there can be from keratosis to verrucous hyperplasia, verrucous carcinoma or OSCC, whether in situ or infiltrating. In order to make the diagnosis of PVL, it was suggested that one of the two following combinations of the criteria mentioned before were met,

1. Three major criteria (Criterion E must be fulfilled) or 2. Two major criteria (Criterion E must be fulfilled) + two minor criteria.

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History

• 59 year old male • Social Hx: -Tobacco, ETOH Socially • Irregular dental care intervals • Previousy 4 & 2 yrs ago • Lesion is spreading to adjacent teeth • Previous Pathology: Focal keratosis

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Malignant Epithelial Pathology

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POMA District VIII 32nd Annual Educational Winter Seminar January 31-February 3, 2019 16 “Benign and Malignant Epithelial Oral Pathology” Edward Halusic, Jr., DMD

Clinical History

• 66 yo male with history of SSC R neck 10 years ago treated with chemoradiation • Now with induration of the left alveolar ridge under denture and with rapid growth

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Verrucous carcinoma Verrucous carcinoma

Treatment and prognosis • Surgical excision without neck dissection • Very low change of • Recurrence depends on ability to excise • 90% disease-free after 5 years

Verrucous carcinoma- Clinical features

• Low-grade variant of SC • Mostly men >55 years old (appears a decade sooner than regular SCC) • Usually large lesion when diagnosed • Painless, slow-growing • Papillary or verrucous surface • Usually white in color, depending on amount of keratin • Mary arise in proliferative verrucous leukoplakia #POMAD8 (PVL) #ChoosePOMA 51

A word about bisphosphonates…..

Complete Dental Exam

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POMA District VIII 32nd Annual Educational Winter Seminar January 31-February 3, 2019 17 “Benign and Malignant Epithelial Oral Pathology” Edward Halusic, Jr., DMD

Thank you!!

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POMA District VIII 32nd Annual Educational Winter Seminar January 31-February 3, 2019 18