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CAUTION

WEETH LECTUURE • Participants should be cautioned about the potential risks of using limited knowledge when integrating new techniques. EARLY ORAL CANCERS AND PRE-CANCERS MARY RIEPMA ROSS THEATER LINCOLN NEBRASKA JANUARY 4, 2019 DONALD M. COHEN DMD, MS, MBA PROFESSOR OF ORAL & MAXILOFACIAL PATHOLOGY ACTING CHAIR DEPARTMENT OF ORAL DIAGNOSTIC SCIENCS UNIVERSITY OF FLORIDA COLLEGE OF DENTISTRY GAINESVILLE, FLORIDA [email protected] 800-500-7585

Conflicts of Interests Course Objectives

• Neither my immediate family nor I have any • Upon completion of this course, participants should be able to: financial interests that would create a conflict of • Recognize and formulate a differential diagnosis, understand the etiology and interest or restrict our independent judgment management of various oral and maxillofacial conditions. with regard to the content of this course. • Better recognize early mailignacies, improve diagnostic skills for oral soft and hard tissue lesions through practice sessions utilizing the audience response devices.

GENERAL DENTIST TO ORAL SURGEON ORAL SURGOEN NOT TO WORRY PLEASE TAKE OUT TWO LOOSE TEETH TWO WEEK FOLLOW UP!!

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IDIOPATHIC

• FEATURES TO WORRY ABOUT • Occurrence in non-smoker • Thickened often corrugated appearance • Associated erythema • High risk location-horseshoe shaped area • ??pain • Multifocal or recurrent

NON-SMOKERS LEUKOPLAKIA TONSILLAR CRYPT EPITHELIUM

• Stratified squamous but basaloid so virus can • 5-8 times INCREASED risk of oral cancer invade epithelium w/o surface ulceration • More frequent on /floor of mouth(64 vs. 11%) • Well known localization for the replication of • More dysplasia(38 vs. 5 %) viruses • Younger patients • Tonsillar crypt epithelium serves as reservoir for • Often very subtle lesions under tongue and on lingual frenum Epstein Barr virus and also HPV • Likely high risk HPV related • Majority of OPSCCA originate from tonsillar epithelium

SEVERE KOILOCYTIC DYSPLASIA

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WHY TALK TO DENTISTS ABOUT HPV??? HPV & ORAL CANCER

• Dentists may be next group of providers to participate in prevention • 70% of sexually active adults are HPV positive of HPV and OPCancer • Prevalence of oral HPV in US population 7% • Improve HPV knowledge and dentists communication skills with • Oro-pharyngeal cancer most common H & N cancer shortly patients • Highlight barriers to discuss HPV with patients • Put HPV vaccination question on dentists patient health history • 47% DDS no discuss HPV with patients • 33% discuss with some patients(papilloma) • 19% Discuss with all patients • JADA 149(1) Jan 2018 pp 9-17

HPV & ORAL CANCER

® 10% male, 3.6% female ® Peak incidence: 30-34 y/o -7.37% 60-64 y/o -11.45%!!! ® HPV-16 incidence 1% (2.13 million people) ® But only 15,000 cases of oropharyngeal cancer/yr

HPV & ORAL CANCER

® Oropharyngeal cancers occur in younger age group. ® Especially troubling increase in non-smoking males with oro- pharyngeal ca ® Men 45 -60 2-3 x more likely to get oro-pharyngeal cancer ® Fortunately HPV associated cancers have a better prognosis ® HPV+HNSCC: Less chromosomal mutations (compared to smoking/ drinking associated tumors)

Ang KK & Sturgis EM. Seminars in Radiation Oncology Volume 22, Issue 2 2012 128 – 142A

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KOILOCYTIC DYSPLASIA TESTING FOR HPV-TISSUE SAMPLES

• HPV-+ cases express high levels p16 tumor-suppressor protein • Diffuse nuclear and cytoplasmic p16 protein-staining correlates strongly with presence of HPV by in-situ hybridization, and PCR.

IDIOPATHIC LEUKOPLAKIA VERRUCO-PAPILLARY HYPERKERATOSIS

• FEATURES TO WORRY ABOUT • Thickened often corrugated appearance • Associated erythema • High risk location-horseshoe shaped area • ??pain • Multifocal or recurrent

(ERYTHROERYTHROERYTHROERYTHRO----)) Leukoplakia

• 82% of transformed leukoplakias • 4 times risk of oral cancer (23.4%)

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ERYTHROPLAKIA ERYTHROPLAKIA

VERY DIFFICULT TO SEE RED ON PINK!! • HISTOLOGIC SPECTRUM: Benign keratosis – 0% Mild dysplasia - 10% Severe dysplasia or ca-in-situ - 40% Invasive carcinoma - 50%

ERYTHROPLAKIA HIGH RISK LOCATIONS ORAL CANCER

• Red lesions should be viewed with suspicion, biopsied. • 90% LOCATED IN: • Suspicious red lesion may be observed for 10-14 days, if persists • LATERAL OR VENTRAL TONGUE biopsy • FLOOR OF THE MOUTH • Recurrence and multifocal involvement are common • LINGUAL FRENUM • Long-term follow-up is needed • SOFT PALATE ANTERIOR PILLAR COMPLEX • FREE AND MARGINAL GINGIVA- ring around the collar

LATERAL BORDER OF THE TONGUE HIGH RISK LOCATIONS ULCER, INDURATED

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VENTRAL TONGUE-ERYTHRPLPLAKIA FLOOR OF THE MOUTH LINGUAL FRENUM

SOFT PALATE / TONSILLAR PILLAR RING AROUND THE COLLAR

HIGH RISK LOCATION PAINPAINPAIN

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4-17-13bx 8-14-13 MULTI-FOCAL papilloma CASE STUDY • This 68 year old female has a three year history of recurring white lesions in her mouth. They have all been diagnosed as hyperkeratosis or atypical epithelial hyperplasia. They keep recurring and spreading to new areas in her mouth.

9-4-`13 01-20-14

1/162 015 09-03-14

What is the most likely diagnosis? Proliferative Verrucous Leukoplakia (PVL) 1. Chemical burn 20% 20% 20% 20% 20% 2. Chronic • Middle aged females(4:1F>M) 3. Candidiasis • Mean age 63.9( over 62) 4. Proliferative verrucous • Little relation to smoking leukoplakia • Little known of etiopathogenesis 5. Squamous cell carcinoma

s urn u sis .. b ia . ma lan d s no cal cou arci mi Candi rru c he ichen p e ll C l v s ce ve u ronic h rati C e if amo l qu ro S P

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Proliferative Verrucous Leukoplakia (PVL)

• Recurrent(av.71%)/persistent • Progresses to multiple sites • ??HPV 16,18 positive ( 0-80%) • High (40-100% av.64%) risk for transformation • Time to transformation 4.7-11.6 years mean 6 years • or squamous • 39% of 277 patients died of within 7 year F/U

Otolaryngol Head Neck Surg 2015 Oct;153(4):504-11

PROLIFERATIVE VERRUCOUS LEUKOPLAKIA Proliferative Verrucous Leukoplakia (PVL)

• No specific treatment modality has proven effective • Laser ablation rapid & high rate of recurrence • 2 not so recent papers no association with HPV • But surgery alone 18/25 recurrences within 6 months • Surgery plus antiviral (anti-HPV immunomodulatory agent) isoprinosine or methisoprinol--2/25 • 18 months post op 2 additional recurrences in anti viral group(4/25) none in surgery group(18/25)

PHOTODYNAMIC THERAPY FOR PVL PHOTODYNAMIC THERAPY FOR PVL

• Innovative non-invasive effective therapy • Low level energy to reactive oxygen species to kill tumor cells • Photochemical reaction induced by laser light • Complete response after 4 sessions • 20% gel of Topical 5-ALA(aminolevulinic acid) • No recurrence for 12 months(n=1) photosensitizer/metabolic precursor • Limited to superficial lesions 1-2 mm • Apply gel for 1.5 hours keep dry • Oral proliferative verrucous leukoplakia treated with photodynamic therapy: a case report. Romeo U et al Annali Stomatologia 2014;V(2);77-80. • 635 nm (low level)laser light to activate photosensitizer • 5, 3 minute and 100 second laser applications(100mW) with 3 minute breaks b/w for each session • Twice a week until resolution

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LOWER LIP NON-HEALING ULCER

CASE STUDY PERIAPICAL LESION????? This 65 year old female complains of mild pain involving the area of the maxillary right first premolar.

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METASTATIC BREAST CANCER METASTATIC BREAST CANCER THREE MONTHE POST EXTRACTION THREE MONTHS POST EXTRACTION

METASTATIC TUMOR TO THE TMJ BONE SCAN METASTATIC TUMOR PROSTATE TO TMJ

METASTATIC TUMORS TO THE JAWS- METASTATIC TUMORS TO THE JAWS SYMPTOMS • Breast 23% Pain • • Lung 15% Swelling • • GI 8% • Loosening of teeth • Male Repro 7% • Presence of a mass • Female Repro 3% • Paresthesia • Renal 3% • Thyroid 3%

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METASTATIC TUMORS TO THE JAWS CASE STUDYCASE STUDY

• Usually present as radiolucent defects. a. One of the 3 P’s • Defect well circumscribed or ill defined ("moth-eaten" appearance). b. Gingival manifestation of • Some carcinomas (prostate and breast), osteoblastic resulting in a systemic disorder radiopaque or mixed radiolucent and radiopaque lesions. c. Peripheral odontogenic neoplasm

d. Malignancy

GRANULOMATOSIS WITH POLYANGIITIS (Formerly Wegener Granulomatosis) 3 FLAVORS OF WEGENER'S • Unknown cause

• Wide age range GRANULOMATOSIS

• No gender predilection • 90% of cases in Caucasians • Generalized Wegener’s Granulomatosis • Can involve almost every organ system in the body • Initial upper & lower respiratory tract and rapid renal • Early stage (before renal involvement) = Strawberry and enlargement of one or more major salivary glands involvement

• Late stage (after renal involvement) = Oral ulcerations Limited Wegener’s Granulomatosis

• Diagnosis: Respiratory tract w/o rapid kidney involvement • PR3-ANCA (previously c-ANCA): Seen in 90-95% of generalized Wegener granulomatosis Superficial Wegener’s Granulomatosis and 60% of early or localized cases Lesions primarily of skin and mucosa • ELISA test for antibodies against PR3 Systemic involvement develops slowly • Mean survival for untreated patients with disseminated disease = 5 months

• 80% of patients die within 1 year and 90% die within 2 years

• Treatment: Oral prednisone and cyclophosphamide

• With appropriate therapy, 75% of patients have prolonged remission

CASE STUDY PRETEST LP OR CANCER? Elderly FM long history of lichen planus and now burning of tongue. DDS in 2002 Dx LP. Spread ventral tongue /1st molar area to second molar all the way anterior. Bx 2007 Ulcer with reactive changes. No evidence of dysplasia or malignancy. Description: Generous biopsy exhibits ulceration with reparative changes including granulation tissue and extensive mixed inflammation. Surrounding epithelium exhibits reactive and regenerative changes. Dysplasia and malignancy are absent. Saw ENT 2011 insists on removal of gold crown on #19 as this is most likely an allergic reaction. Pt never smoked Middle aged female with irregular white and red lesion on right buccal mucosa for 3 years

5/10/2011

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PRETEST LP OR CANCER? HISTOLOGIC OVERLAP

I have a patient I have been seeing for • 29% OF DYSPALSTIC AND MALIGNANT ORAL LESIONS HAD 3 OR some time. Originally presented with MORE OF THE FIVE HISTOLOGIC FEATURES OF LICHEN PLANUS well localized erythematous lesion of palate. A biopsy prior to my evaluation Dx: lichen planus. Did another biopsy 2009 and immunoflourescence confirmed diagnosis. Treated her with clobetasol ointment and diflucan to no avail. I'm not sure I'm actually dealing with 'run of the mill' lichen planus and would like you to take a look. I've attached a few pictures from September.

PRETEST LP OR CANCER? APRIL 2009 PRETEST LP OR CANCER?

Middle aged female biopsy proven lichen planus. Biopsied 4x over the last few years 1 biopsy showed LP with atypia. Has been using topical steroid in area every day for 1 year.

Epidemiology Lichen planus Oral Lichen Planus has distinctive • Common mucocutaneous disorder- 2% of population. clinical features and classical • Increasing frequency distribution… or does it?? • Disease of middle aged and elderly. • More common in females.

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LICHEN PLANUS

• 90% of patients have bilateral reticular lesions in the posterior buccal mucosa. • The tongue is the next most commonly involved followed by the gingiva and alveolar ridge.

Reticular Lichen Planus EROSIVE LICHEN PLANUS

Factors in the Etiopathogenesis of FOREIGN BODY GINGIVITIS LichenOID MUCOSITIS

• Drug induced • Foreign body (gingiva) – prophy jet • Dental materials

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DENTAL MATERIALS AMALGAM REMOVED 3 MONTHS AGO Hi Dr Cohen my patient has a very persistent lichenoid lesion on his tongue that I have been treating unsuccessfully for a couple of years.

TRIGGERS of LichenOID MUCOSITIS/Lichen Planus STAY

• Reduce stress • ? Stress • Exercise 5x week for 30 minutes • Trauma • Must sweat to be effective • Aspirin( actually NSAID’s /Amalgam • Yeast • Idiopathic (true lichen planus)

TRAUMA KOEBNER PHENOMENON

• Triggers the condition in susceptible • Development of isomorphic pathologic lesions in the traumatized uninvolved skin of patients who have cutaneous disease individuals

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TRAUMATIC LICHENOID MUCOSITIS TRAUMATIC LICHENOID MUCOSITIS

TRAUMATIC LICHENOID MUCOSITIS A

• Aspirin (actual NSAIDS) • Amalgam

Drugs Implicated in Oral Lichenoid Reactions Category Drugs Implicated in Oral Lichenoid Reactions Category Drugs – Drugs Cont.

Antimicrobials • Dapsone • Ketoconazole Antiarthritics • Aurothioglucose • Para-aminosalicylic acid • Colloidal gold (Europe only) • Sodium aminosalicylate • Gold sodium thiomalate and thiosulfate • Streptomycin Sparfloxacin • • Lorazepam • Sulfamethoxazole, Sulfasalazine • Tetracycline Anxiolytics • Fenclofenac • Ibuprofen • Antimony compounds (stibophen, stibocaptate) • Naproxen • Organic arsenicals Non-Steroidal Anti-inflammatory Agents • Phenylbutazone • Chloroquine Antiparasitics • Pyrimethamine • Quinacrine • Chlorpropamide • Tolazamide • ACE inhibitors -Captopril • Tolbutamide • Chlorothiazide, Hydrochlorothiazide • Labetalol, Practolol, Propanolol • Allopurinol Lasix • Hypoglycemic agents • Mercurial diuretics Antihypertensives • Methyldopa

Uricosurics

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Drugs Implicated in Oral Lichenoid Reactions Category Drugs – Cont. Drug Induced

Miscellaneous • Amitriptyline • Clopidrogel (Plavix) • Imipramine • Often erosive • Iodides Lithium • Omeprazole • Penicillamine, Procainamide • May involve the lips • Phenytoin • Quinidine Sulfate • Sildenafil (Viagra) • Often asymmetric • Paraphenylenediamines used in color film developers • Dental composite filling materials • Dental casting alloys and amalgam restorations Dental Materials • Simvastatin • Gemfibrozil

Lipid Lowering

LICHENOID DRUG ERUPTIONS Lichenoid Drug Eruption

• Takes an average 12 months to develop. • Can develop after 10years on same drug • Ebbs and flows while on drug • May take up to 24-months to clear. • Usually improves in 2-8 weeks..

YEAST Yeast + Lichen Planus

• Red, fuzzy lesion • Exacerbate the condition

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Differentiate Lichenoid Mucositis from OLM vs. Dysplasia Dysplasia • Biopsy not always conclusive!!! • Short term topical steroid Tx. • Pre-cancerous lesions worsen, become more defined erythro-, or leukoplakic • OLM lesions improve/disappear • Asymmetry of lesions is key for dysplasia

+ Topical steroids for 2 weeks Treatment

• Not entirely satisfactory • No cure available • Immune suppression is the key • Only 1 out of 15 resolve spontaneously.

Lichen Planus Treatment

• Clobetasol gel 0.05% • Dsp. 15 or 30 gm. Topical steroids are the mainstay • Sig. apply sparingly b.i.d. of therapy. • Very strong use for Tx initiation

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TREATMENT 2 WEEKS TOPICAL CLOBETASOL

• BEFORE • AFTER

Lichen Planus Treatment Lichen Planus Treatment

• Lidex gel 0.05% • Stringent oral hygiene and • Dsp. 15 or 30 gm. prophylaxis procedures Q 3-6 months. • Sig. Apply sparingly 3-4 times a day. • Good for long term treatment

Follow-up

Sulcabrush once a day every day • Patients must be seen 1-2 times a year. • Return if condition worsens. • Erosive / atrophic types much more risky. • Biopsy IF lesions change clinical appearance or resist Tx.

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POSTTEST LP OR CANCER? POSTTEST LP OR CANCER?

5/10/2011 8/12/2013 I have a patient I have been seeing for some time. Originally presented with well localized erythematous lesion of palate. A biopsy prior to my evaluation Dx: lichen planus. Did another biopsy March of 2009 and immunoflourescence confirmed diagnosis. Treated her with clobetasol ointment and diflucan to no avail. I'm not sure I'm actually dealing with 'run of the mill' lichen planus and would like you to take a look. I've attached a few pictures from September.

POSTTEST LP OR CANCER? 2 WEEKS LOTRISONE TREATMENT • Middle aged female with biopsy proven lichen planus. Biopsied 4x over the last few years 1 biopsy showed LP with atypia. Has been using topical steroid in area every day for 1 year.

APRIL 2009 POSTEST LP OR CANCER? JANUARY 2010

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Dear Pathologist, Here are some photos of an elderly woman that takes the following meds: atenolol, Fosamax, Coumadin, and simvastatin. She has swelling of the entire upper lip for past 10 days increasing in size. No tenderness or pain. Ulceration on the right is indurated and no purulence on exam. Denies trauma. I'm thinking angioneurotic edema and placed her on Magic Mouth wash and will see her again in one week. I thought the lesion looked interesting. Hope you are well, Sincerely,

Oral Surgeon

1 week later……

Diagnosis Anaplastic Large Cell Lymphoma ALK Negative

Anaplastic Large Cell Lymphoma • A rare form of indolent Non-Hodgkin’s lymphoma ALK-Negative (ALCL, ALK-) • Peak incidence in adults (40-65 yrs.) but can occur at any age

• Slight male preponderance (1.5:1)

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2 weeks post biopsy

2 weeks post- operatively….

EB Virus Positive B-cell Lymphoproliferative POST TRANSPLANT LYMPHOPROLIFERATIVE Disorder (E-LPD) DISEASE

• E-LPD) spectrum of lymphoid expansion entities caused by • Can be self limited with decreased immunosuppression or go on to be immunosuppression or immunosenescence and associated with full blown monoclonal lymphoma. Epstein-Barr virus. • Therefore early diagnosis is critical • Immunosenescence seen in 65+ y/o • 1/3 involve the H & N • Immunosuppression can be post transplant or with any use of • Oral cavity is often the first place lesions appear. immunosuppressive drugs • First sign is lymphadenopathy then destructive lesions( recalcitrant oral ulcers), ranging up to florid neoplasia with aggressive behavior

POST TRANSPLANT LYMPHOPROLIFERATIVE CASE STUDY DISEASE 70y/o male painful gingival ulcer. Present 3 months and is not healing despite root planning and excision. History of kidney transplant in 2104 • E-LPD second most common form of neoplasia in solid organ transplant patients • Important early cause of cancer related death and graft loss. • Distinct clinicopathologic entity first described in the oral cavity as recalcitrant destructive EBV+ oral ulcers in 2010

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CASE STUDY PTLD Teen male C.C. pain and drainage lower jaw. Seen in several emergency departments for jaw swelling and • 1/3 of cases in H & N drainage. Treated 10 years ago with both chemo and • Second most common form of neoplasia in solid organ transplant radiation therapy for bilateral cancer of his hips patients • Early cause of cancer related death and graft loss • First sign lymphadenopathy then destructive lesions

RADIOGRAPHIC FINDINGS Extensive osteolytic expansile lesion left mandibular body and left maxilla LANGERHANS CELL DISEASE (Histiocytosis X; Eosinophilic Granuloma

• Histiocytosis X: spectrum of clinicopathologic disorders characterized by proliferation of histiocyte-like cells and eosinophils. • Now considered clonal neoplastic process involving myeloid dendritic histiocytic cells • This disorder is characterized by single or multiple osteolytic bone lesions

CLINICO-PATHOLOGIC SPECTRUM LANGERHANS CELL DISEASE

• Wide age range with patients being reported even in the 6th and • Eosinophilic granuloma of bone- one or more 7th decades. lesions w/o visceral involvement • 50%+ seen under age 10. • Hand-Schüller-Christian disease- chronic disseminated bone, skin, viscera • 55% single system disorder with bone lesions solitary or multiple, most common clinical presentation. • Letterer-Siwe disease- acute disseminated with prominent cutaneous, visceral, and bone involvement, in infants

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LANGERHANS CELL DISEASE LESIONS OF ALVEOLAR PROCESS

• Skull, ribs, vertebrae, mandible most frequent sites. • Jaws affected in 30% skull 21% of adults. • Most common lesions in oral cavity are teeth floating in air, gingivitis/periodontitis, unexplained mass or mucosal ulcers

RESEMBLES AGGRESSIVE TEETH FLOATING IN AIR

LANGERHANS CELL DISEASE TREATMENT LANGERHANS CELL DISEASE

• Clinical course quite varied depending on age and stage of the disease • Single agent treatment such as prednisone • Pts with multi-focal disease respond initially to intralesional and or systemic, prednisone treatment but often recur same or distant site combined with vinblastine and/ or curettage of readily accessible bone lesions. • The bilateral cancer in this patient’s hips was actually LCH which has recurred 10 years after • Low dose radiation for less accessible lesions. initial remission

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CASE STUDY

Middle aged FM 1 yr. hx. progressive tongue enlargement Progressively worsening posterior open bite Possibly related to tongue enlargement but hard for me to attribute all this to the tongue Recurrent, episodic, purple lesions and sores on the tongue

MY ASSESSMENT

• Judging from wear pattern in teeth something opened up vertical. • Heterogeneous group of conditions characterized by deposition • Assume condyles are normal and her thyroid function. of extracellular material called amyloid. • I think acquired macroglossia from vascular malformation/hemorrhagic • Amyloid associated with: multiple myeloma, rheumatoid diathesis, amyloid accumulation or clotting disorder arthritis or chronic infections including tuberculosis. • If tall evaluate for Beckwith-Weidman syndrome. • Other signs of bruising or clotting problems on the skin??

SYSTEMIC AMYLOIDOSIS Primary & Myeloma-Associated Amyloidosis • Occurs in several forms: Affect older adults (av. 65) • primary • • myeloma-associated • Mucocutaneous lesions and macroglossia from amyloid deposits • secondary • hemodialysis-associated • Macroglossia 12-40%, diffuse or nodular enlargement of tongue. • heredofamilial

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MYELOMA TREATMENT TREATMENT SIDE EFFECTS

• Multiple drugs • 81% infections • Dexamethasone • Blood clots • I.V. Bisphosphonates • Thrombocytopenia • Proteases inhibitors(Velcade) • Monoclonal antibodies(attack CD-38) • MRONJ • Melphalan-nitrogen mustard alkylating agent • Low blood counts Immune modulating drugs • • Mouth sores • Lenalidomide(revlimid)

CASE HISTORY • This 40’s y/o male pain and swelling (purplish mass) in posterior mandible. Second premolar and first molar teeth tested non vital and pulps of both teeth were necrotic.

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Patient with history of myeloma now with CASE STUDY soft tissue mass HARD PALATE • 57 y/o Cauc male 5 cm x 3 cm spongy mass hard palate. Lesion first noted by hygienist. • Patient reluctant to have biopsy because asymptomatic and had multiple similar “lipomas” on his back. • Lesion did not blanch with pressure. Swelling did not communicate with teeth

DIAGNOSIS: MANTLE CELL LYMPHOMA NON-HODGKIN'S LYMPHOMA

• One of four types of small B-cell lymphomas • Occurs primarily in adults • Distinct subtype due to short survival and aggressive course • Makes up 5% of oral malignancies • Predilection for elderly males, hard palate • Second most common malignancy of oral cavity • Treatment: chemotherapy(RCHOP), radiation and possible BMT • Nontender slowly enlarging mass involves cervical, axillary or inguinal nodes

ORAL NON-HODGKIN'S LYMPHOMA

• Nontender, diffuse soft tissue swellings of buccal vestibule, gingiva, or posterior hard palate. • Appear erythematous or purplish and have "boggy" consistency.

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CASE HISTORY • This 30’s female lump in palate for 2 yrs. Asked her DDS about it . He referred her to ENT specialist who diagnosed normal anatomy. Developed headaches and given therapy for TMD. Recently returned to her dentist who noticed the lump and referred her to me for a second opinion.

POLYMORPHOUS ADENOCARCINOMA MINOR SALIVARY GLAND TUMORS

• Recently recognized -1983 • Almost 50% malignant • Almost exclusively in the minor SG • “Smaller the gland, the greater the chances of malignancy" • 60% hard or soft palate,16% BM, 12% upper lip • Palate - most frequent site (42 to 54%) • 2/3rds in females • Posterior lateral hard or soft palate • Lips- second most common

POLYMORPHOUS ADENOCARCINOMA

• Tumor cells have uniform appearance • Different growth patterns hence, "polymorphous“ • Perineural invasion common • Wide surgical excision • Overall prognosis relatively good, 80% cure rate

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CASE STUDY CASE STUDY Tooth #18 area Retro-molar pad area 30’s male pain in area of tooth #18 and paresthesia lower lip 4 weeks duration. Root canal therapy and antibiotic did not relieve pain/paresthesia. Referred to a periodontist who did RP & S. Then referred to Dr Cohen for consult. Dr Cohen recommended oral surgeon do a biopsy. Diagnosis???

LOW GRADE CHONDROBLASTIC OSTEOSARCOMA (Osteogenic Sarcoma) OSTEOSARCOMA • Most common primary malignant tumor of bone. • Important early radiographic change symmetric • Distal femur and proximal tibia are most frequent sites widening of periodontal ligament space. • Only 7% occur in jaws. • When combined with pain/discomfort and other radiographic changes important in early diagnosis • Mean age for jaw 33, (10-15 years older than for long bones) • Lip paresthesia is key diagnostic feature • See paresthesia only with malignancy and osteomyelitis • Radical surgery preceded by chemo and radiation most common Tx.

OSTEOSARCOMA OSTEOSARCOMA

• Swelling(100%) and pain(5%) most common symptoms. • Local uncontrolled disease cause of death>> than distant • Peripheral border ill defined and indistinct. metastases. • Spiking resorption of roots of teeth • Jaw osteosarcomas lesser tendency to metastasize • “Classic" sunburst or sun-ray 25% of jaw osteosarcomas • Metastases most often involve lungs and brain. • 80% survival rate for jaw lesions with radical surgery alone(3cm margins). • Long bone lesions chemo, radiation and surgery

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CASE STUDY

This 20’s y/o female dull ache and swelling right posterior mandible. Lesion present for just three weeks according to the patient.

CASE STUDY ACUTE MYELOGENOUS LEUKEMIA

Middle aged female 3-4 week • Begins with malignant transformation of stem cell, history of swollen gums. DDS sent her to 2 MDs who Rx proliferates in bone marrow and eventually overflows antibiotics w/o improvement. into peripheral blood She is very tired all the time. DDS sent her to a periodontist who • Leukemic cells "crowd out" normal defense cells and does biopsy erythrocyte precursors.

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LEUKEMIA LEUKEMIA

• Classified according to their histogenesis and clinical • Acute leukemias- untreated, aggressive course and behavior result in death within a few months (survival is < six • Myeloid(granulocyte/monocytes)or lymphocytic months). (histogenetic origin) • Chronic leukemias more indolent course, but end • Broad category would be acute or chronic (clinical result is same (chronic - survival over one year). course)

LEUKEMIA LEUKEMIA

• Certain types of leukemia show specific chromosomal • Environmental agents increased risk- benzene, abnormalities ionizing radiation & HTLV-1 • Chronic myeloid leukemia (CML)- genetic alteration, • Myeloid leukemias affect adults Philadelphia chromosome, translocation of • Acute myeloid leukemia (AML) broader age range chromosomal material between long arms of including children. chromosomes 22 and 9. • Chronic myeloid leukemia (CML) third and fourth decades.

LEUKEMIA LEUKEMIA • Chronic lymphocytic leukemia (CLL) most common type in adults, affects • Acute leukemia-abrupt onset elderly adults median age 60. • Clinical signs and symptoms- accumulation of • 24% of all leukemias neoplastic cells in marrow causes marked reduction in • Acute lymphoblastic leukemia (ALL) normal white and red cells occurs in children(2-3), most common • Causes infections and anemia respectively childhood malignancy.

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LEUKEMIA LEUKEMIA

• Spontaneous gingival hemorrhage, result of decreased • Complain of easy bruising and platelet counts,<10-20,000mm3 (thrombocytopenia). bleeding. • Fever associated with infection may be initial sign • Petechial hemorrhages posterior hard and soft palate due to thrombocytopenia

LEUKEMIA

• Oral ulcers often present- due to impaired ability to combat normal flora. • Gingival tissues most severely affected because of abundant plaque around teeth.

LEUKEMIA LEUKEMIA

• Leukemic cells infiltrate soft tissues- most frequent • Diagnosis is established by finding poorly with myelo-monocytic types differentiated leukemic cells in peripheral blood and • Results in diffuse . bone marrow. • Treatment consists of various forms of chemotherapy.

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LEUKEMIA PROGNOSIS

• Depends on type and age of patient. • In children with ALL- 95% complete remission, 75-85%% cured • Adults similar 80% response rate but much lower cure rate(35-40%)

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