Oral Cancer and Potentially Malignant Lesions Contact Information

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MAOMS Seminar June 9, 2016 Oral Malignancies and Mimics

Mark A. Lerman, D.M.D. Associate Professor and Division Director of Oral Pathology Tufts University School of Dental Medicine Oral Malignancies and Mimics • Red, White, and Blue Lesions of the Oral Cavity

• Oral Cancer and Potentially Malignant Lesions Contact Information

• Mark A. Lerman, D.M.D. • Email: [email protected] • Website: http://dental.tufts.edu/TOPS • Appointments: 617-636-3932 Oral Malignancies and Mimics • Red, White, and Blue Lesions of the Oral Cavity

• Oral Cancer and Potentially Malignant Lesions Red Lesions

• Periodontal disease • Benign migratory glossitis • Inflammatory gingival nodules • Desquamative gingivitis • Localized juvenile spongiotic gingival hyperplasia • Erythroplakia Red Lesions

• Geographic tongue/ Erythema migrans • Common immune-mediated condition • One or more erythematous patches incompletely bordered by white-yellow peripheries • Involves dorsal, lateral or ventral tongue – Ectopic geographic tongue seldom seen Benign Migratory Glossitis

• Clinical or microscopic diagnosis • Generally asymptomatic • Topical Benedryl or steroid may be considered for rare symptomatic cases Red Lesions

– Pyogenic granuloma – Peripheral giant cell granuloma – Peripheral ossifying fibroma Pyogenic Granuloma

• common poorly-named reactive lesion of oral cavity – neither pyogenic nor a granuloma • may be seen in pregnant women (“pregnancy tumor”) Peripheral Giant Cell Granuloma

• common pseudotumor of oral cavity • reaction to irritation or trauma • soft tissue counterpart of central giant cell granuloma Inflammatory Gingival Nodules

• Treatment and Prognosis – local excision down to periosteum to minimize recurrence – if central giant cell granulomas cannot be excluded, rule out hyperparathyroidism Red Lesions

• NOT a diagnosis • Clinical term to describe a manifestation of what is usually lichen planus, a hypersensitivity reaction, or mucous membrane pemphigoid Desquamative Gingivitis

• Lichen planus • Contact reactions • Mucous membrane pemphigoid • Pemphigus vulgaris Oral Lichen Planus

• Clinical Features – Reticular – Erosive/erythematous – Ulcerative Lichen Planus • associated with: – NSAIDs – anti-hypertensive agents – anti-hyperglycemic agents – cholesterol lowering agents – thyroid medications – anti-gout medications – amalgam restorations – cinnamon flavoring agents – herbal remedies Lichen Planus

• Treatment – Fluocinonide or clobetasol gel 0.05% • Apply to affected area QID • Dispense one 15g tube • Warn patient – Dexamethasone elixir • Dispense: 240 cc • Swish for 5 minutes and expectorate QID – Monitor for candidiasis – Follow-up Mucous Membrane Pemphigoid

• Antibodies to hemidesmosomes • Twice as common as pemphigus vulgaris • Average age= 50-60 • Female predilection= 2:1 Mucous Membrane Pemphigoid

• Treatment – Topical steroids for oral lesions – Refer to ophthalmology Technical Considerations

• When considering vesiculobullous disease… – Always include intact epithelium – Submit separate biopsies in: • 10% formalin for H&E • Michel medium for DIF – Defer empiric treatment, if possible, until after biopsy is complete Pemphigus Vulgaris

• Potentially life-threatening skin and mucous membrane disease • Incidence= 1-5 per million • Average age at diagnosis= 50 • Antibodies to desmosomes • Usually seen over 50 years of age • No gender predilection • More common in people of Ashkenazi Jewish descent Pemphigus Vulgaris

• Treatment and Prognosis – Corticosteroids – Azathioprine – Immunoglobulin therapy – Untreated, mortality approaches 80% Red Lesions

• Unique pattern of gingival hyperplasia UNRELATED to dental plaque • Originally described by Darling et al. in 2007; since reported by Chang et al. in 2008 LJSGH

• Most cases between ages 5-15 • Predilection for anterior facial gingiva • Asymptomatic • Bright red raised overgrowths, sometimes with papillary architecture Red Lesions

• Red patch or plaque that cannot be characterized clinically or pathologically as any other disease • Uncommon, but HIGHLY suspicious for malignancy White Lesions

• Leukoedema • Candidiasis • Squamous papillomas • Lichen planus • Chronic frictional keratoses • Leukoplakia White Lesions

• Leukoedema • Candidiasis • Squamous papillomas • Lichen planus • Chronic frictional keratoses • Leukoplakia Leukoedema

• Generalized opalescence of the mucosa • Most commonly involves buccal mucosa • More common in African-Americans and smokers • Disappears when mucosa is stretched Leukoedema

• Clinical diagnosis • No treatment White Lesions

• Leukoedema • Candidiasis • Squamous papillomas • Lichen planus • Chronic frictional keratoses • Leukoplakia Candidiasis Patterns

• Acute – Pseudomembranous candidiasis (thrush) – Acute atrophic candidiasis • Chronic – Chronic atrophic candidiasis – Hyperplastic candidiasis – Angular cheilitis – Median rhomboid glossitis Pseudomembranous Candidiasis

• White plaques • May or may not wipe away, leaving red, raw surface exposed Median Rhomboid Glossitis

• Etiology unclear – Developmental vs. infectious • Flat/slightly raised erythematous rhomboid area of midline dorsal tongue Acute Atrophic Candidiasis

• Erythematous candidiasis often associated with antibiotic use • Often involves midline palate Chronic Atrophic Candidiasis

• Often associated with chronic denture wear – Involves gingiva in direct contact with removable prostheses • May be referred to as “denture stomatitis” Chronic Hyperplastic Candidiasis

• Controversial variant • White plaques that cannot be scraped away • True leukoplakia with secondary colonization? Angular Cheilitis

• Erythema or fissuring of commisure(s) • Candidal infection, often with co-infection by staph and/or strep • May be associated with loss of vertical dimension and/or salivary pooling Anti-Fungal Therapy

• Polyenes – Nystatin – Amphtericin B • Imidazoles – Clotrimazole – Ketoconazole • Triazoles – Fluconazole – Itraconazole Anti-Fungal Therapy •Topical therapy

•Clotrimazole 10 mg •Dispense (30-40, write exact number) troches •Dissolve one tablet in mouth 3-4x/day for two weeks

•Nystatin suspension 1:100,000 iu/ml •Dispense (200-300, write exact amount) ml •Swish and expectorate (or swallow if necessary) 5 ml 3-4 x/day for two weeks Anti-Fungal Therapy •Topical therapy

•Vytone 1% (hydrocortisone-iodoquinol) cream •Dispense 15 or 30 g (write exact number) tube •Apply to affected site 3-4x/day for two weeks

•Mycolog II cream (nystatin-triamcinolone) •Dispense 15 or 30 g (write exact amount) tube •Apply to affected site 3-4x/day for two weeks Anti-Fungal Therapy •Systemic therapy

•Fluconazole 100 mg tablets •Dispense 3-7 (write exact number) tablets •Take one tablet in the morning x 3-7 days White Lesions

• Leukoedema • Candidiasis • Squamous papillomas • Lichen planus • Chronic frictional keratoses • Leukoplakia Squamous Papilloma

• Papillary mass • Benign proliferation of stratified squamous epithelium • Induced by human papillomavirus – HPV types 6 and 11 found in half of oral papillomas Squamous Papilloma

• Treatment and Prognosis – Conservative surgical excision (including base of lesion) – Recurrence unlikely White Lesions

• Leukoedema • Candidiasis • Squamous papillomas • Lichen planus • Chronic frictional keratoses • Leukoplakia Frictional Hyperkeratosis

• Chronic biting injury • Benign alveolar ridge keratosis (BARK) • Non-specific White Lesions

• Leukoedema • Candidiasis • Squamous papillomas • Lichen planus • Chronic frictional keratoses • Leukoplakia Leukoplakia

. Well-defined vs. Poorly-defined Borders . Localized vs. Multi-focal . Homogenous vs. Heterogenous . Speckled . Nodular . Verrucous Proliferative Leukoplakia

• Proliferative verrucous leukoplakia • Multifocal leukoplakia that recurs with a tendency to undergo malignant transformation • Female predilection? • Less often associated with a history of tobacco or alcohol use Blue and Pigmented Lesions

• Foreign material • Melanin • Vascular structures • Saliva • Cystic fluid Blue and Pigmented Lesions

• Foreign material • Melanin • Vascular structures • Saliva • Cystic fluid Pigmented Lesions • Exogenous Pigmentation • Endogenous Pigmentation Exogenous Pigmentation Amalgam Tattoo

• Black-blue-gray macule • Often appears on gingiva adjacent to restorations – May appear on any mucosal surface Heavy Metal Toxicity

• Lead • Mercury • Silver • Bismuth • Gold Heavy Metal Toxicity

• Pigmentation of marginal gingiva • Tongue tremor • Metallic taste • Excessive salivation • Trichotillomania • Bruxism Endogenous Pigmentation

• Etiology – Developmental – Reactive – Neoplastic Endogenous Pigmentation • Etiology – Developmental • Physiologic • Genetic – Reactive • Oral melanotic macule • Post-inflammatory hyperpigmentation • Melanoacanthosis • Medication-related – Neoplastic • Nevus • Melanoma Endogenous Pigmentation • Etiology – Developmental • Physiologic • Genetic – Reactive • Oral melanotic macule • Post-inflammatory hyperpigmentation • Melanoacanthosis • Medication-related – Neoplastic • Nevus • Melanoma Conditions with Oral Pigmentation

• Peutz-Jeghers syndrome • Neurofibromatosis • McCune-Albright syndrome • Addison disease • Laugier-Hunziker syndrome Peutz-Jeghers Syndrome

• Autosomal dominant condition – Mutation of STK11/LKB1 gene – Freckle-like lesions of the hands, peri-oral region, and/or oral mucosa – Intestinal polyposis with predisposition to adenocarcinoma

Higham P, Alawi F, Stoopler ET. Medical management update: Peutz Jeghers syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;109:5–11.

Shah KR, Boland CR, Patel M, et al. Cutaneous manifestations of gastrointestinal disease: part I. J Am Acad Dermatol 2013;68:189.e1–21. Neurofibromatosis • Eight forms, most common is Type I – Von Recklinghausen disease – Autosomal dominant – Mapped to chromosome 17 • Characteristic features – Multiple neurofibromas – Café au lait pigmentation – Crowe sign – Lisch nodules McCune-Albright Syndrome

• Variant of polyostotic fibrous dysplasia – Developmental condition resulting from GNAS1 mutation • Associated with café au lait macules and endodrinopathies Addison Disease

• Hypoadrenocorticism, adrenal insufficiency • Insufficient production of adrenal corticosteroids • Diffuse or patchy hyperpigmentation, especially of sun-exposed skin Laugier-Hunziker Syndrome

• Rare acquired diagnosis of exclusion – Macules of the labial and/or buccal mucosa – Longitudinal streaks in fingernails Endogenous Pigmentation • Etiology – Developmental • Physiologic • Genetic – Reactive • Oral melanotic macule • Post-inflammatory hyperpigmentation • Melanoacanthosis • Medication-related – Neoplastic • Nevus • Melanoma Oral Melanotic Macule

• Benign pigmented macule • Most common on lower lip • Traumatic? Smoker Melanosis

• Post-inflammatory hyperpigmentation • Facial gingiva affected most often • May be seen in 20% of smokers Lichen Planus

• Chronic immune-mediated disease • May exhibit post-inflammatory hyperpigmentation Oral Melanoacanthosis

• a.k.a. oral melanoacanthoma • Rare acquired pigmented lesion(s) of rapid onset • Reactive? • Predilection for African-American females ages 20-40 • May reach several cm in size Drugs Associated with Oral Hyperpigmentation

• Minocycline • Anti-malarials • Kinase inhibitors • Psychotropic Medications • Oral contraceptives • Antiarrhythmics Endogenous Pigmentation • Etiology – Developmental • Physiologic • Genetic – Reactive • Oral melanotic macule • Post-inflammatory hyperpigmentation • Melanoacanthosis • Medication-related – Neoplastic • Nevus • Melanoma Melanocytic Nevi

• Benign developmental malformations

• Variants include: – Acquired nevus – Congenital nevus – Blue nevus – Spitz nevus Oral Melanoma

• Rare malignancy accounting for <1% of all melanomas • May be associated with mutations in BRAF gene involved in Ras- Rad-ERK signaling pathway Oral Melanoma

• Predilection for African- Americans, Asians, and Hispanics • 80% develop on gingiva or hard palate • Pigmented macule, nodule, mass, or plaque • In-situ and invasive subtypes Melanoma vs. Melanocytic Nevus

• Asymmetry • Borders • Color • Diameter • Evolving Oral Melanoma

• Biopsy mandated for all suspicious pigmented lesions • Sampling of nodular or darkly pigmented foci for non- homogenous lesions • Role for sentinel node biopsy?

Starek I, Koranda P, Benes P. Sentinel lymph node biopsy: A new perspective in head and neck mucosal melanoma? Melanoma Res. 2006 16(5) 423-7 Oral Melanoma

• Stage I – localized disease • Stage II – regional nodal involvement – 25% of oral melanoma at diagnosis • Stage III – distant metastasis

Patel SG, Prasad ML, Escrig M, et al. Primary mucosal malignant melanoma of the head and neck. Head Neck. 2002; 24:247-57 Oral Melanoma • Treatment • Surgery • Limited role for radiation • Chemotherapy? • 5 year survival ~10-20%

McLean N, Tighiouart M, Muller S. Primary mucosal melanoma of the head and neck. Comparison of clinical presentation and histopathologic features of oral and sinonasal melanoma. Oral Oncol 2008;44:1039–46.

Postow M, Hamid O, Carvajal R. Mucosal melanoma: Pathogenesis, clinical behavior, and management. Curr Oncol Rep. 2012; 14:441-8. Melanotic Neuroectodermal Tumor of Infancy

• Rare tumor developing within first year of life • Predilection for anterior maxilla • Presents as expansile blue-black mass • Associated with high levels of vanillylmandelic acid • Mostly benign; 20% recur Oral Pigmented Lesions • Exogenous Pigmentation • Endogenous Pigmentation – Developmental – Reactive – Neoplastic In Conclusion…

• High risk locations differ depending on color and suspected clinical diagnosis • Red lesions more rare BUT more worrisome than white lesions • Oral pigmented lesions considered melanoma until proven otherwise • Multi-focal pigmented lesions may suggest systemic etiology MAOMS Seminar June 9, 2016 Oral Malignancies and Mimics

• Oral Cancer and Potentially Malignant Lesions Oral Malignancies and Mimics • Red, White, and Blue Lesions of the Oral Cavity

• Oral Cancer and Potentially Malignant Lesions Oral Cancer

• Oral cancer • Diagnostic techniques • Biopsy procedure Biopsy of Mucosal Lesions

• Oral cancer • Diagnostic techniques • Biopsy procedure Leading Causes of Death in USA

• Heart Disease 25% • Cancer 23% • Cerebrovascular Disease 6% • Respiratory Disease 5% • Accidents 5% • Alzheimer Disease 3% • Diabetes Mellitus 3%

US Mortality Data 2007, National Center for Health Statistics, Centers for Disease Control and Prevention, 2010 Oral/Pharyngeal Cancer

48,330 ESTIMATED NEW CASES in 2016

• 9,570 estimated deaths • Incidence more than twice as high in men • 3% of all cancers • 8th most common type of cancer diagnosed • Overall 5 year survival rate = 62% • Mortality rate improved slightly in last 50 years

American Cancer Society, Cancer Facts and Figures 2015 Clinical Staging

Clinical Stage 5 year survival

Stage I T1N0M0 85% Stage II T2N0M0 66% Stage III T3 or any T w/ N1 41% Stage IV T4 or any T w/ N2 or M1 9% Oral Cancer • Squamous cell carcinoma • Everything else – Lymphoma – Salivary gland malignancies – Bone and soft tissue sarcomas – Melanoma – Odontogenic tumors – Metastasis Clinical Presentation of Oral Squamous Cell Carcinoma • Leukoplakia • Erythroplakia • Non-healing ulceration • Exophytic mass Etiology of White Lesions

• Developmental • Infectious • Immune- mediated • Reactive • Neoplastic/ Dysplastic Leukoplakia White patch or plaque that cannot be characterized clinically or pathologically as any other disease Leukoplakia

Waldron & Shafer analyzed 3,256 cases:

80% Hyperkeratosis +/- hyperplasia 12% Mild to moderate dysplasia 4% Severe dysplasia or ca-in-situ 3% Squamous cell carcinoma Proliferative Leukoplakia

• Multifocal leukoplakia that recurs with a tendency to undergo malignant transformation • Female predilection • Not associated with a history of tobacco or alcohol abuse Erythroplakia

Waldron & Shafer analyzed 58 cases

9% Mild to moderate dysplasia 40% Severe dysplasia or ca-in-situ 51% Squamous cell carcinoma Leukoplakia and Erythroplakia • Biopsy of all lesions present for more than two weeks

• Complete excision of unexplained lesions in high risk areas regardless of histology

• Complete excision of dysplastic lesions and long term follow-up Oral Epithelial Dysplasia

Microscopic features • Basilar hyperplasia • Tear-drop shaped rete ridges • Loss of normal stratification • Nuclear enlargement & hyperchromaticity • Cellular pleomorphism • Increased mitotic activity • Dyskeratosis Oral Epithelial Dysplasia

Mild • lower 1/3 of the epithelium Moderate • lower 2/3 of the epithelium Severe • greater than 2/3 of the epithelium Carcinoma-in-situ • full-thickness of epithelium Risk Factors • Tobacco • Alcohol • Human papillomavirus infection • Immune suppression • History of cancer • Family history of cancer • Areca nut • Actinic damage Tobacco

• Risk of dysplasia increases with amount of smoking

• Risk is 4-8x that of non-smokers

• Risk declines with time since cessation of smoking Alcohol

• Risk of dysplasia 2-4x greater than in nondrinkers Tobacco and Alcohol

• Effects are synergistic

• Selected studies show people who smoke and drink have 30x increased risk Human Papillomavirus

• Low risk types • HPV 6 & 11 • Squamous papillomas

• High risk types • HPV 16 & 18 • HPV-associated oral epithelial dysplasia Oral Squamous Cell Carcinoma

• Male:female ratio = 2.5:1

• Average age at diagnosis = 62

• Increasing incidence before age 40 Oral Squamous Cell Carcinoma

Field cancerization • Patients with one oral carcinoma have an increased risk for additional oro-pharyngeal carcinomas

• 35% of patients with oral cancer develop another primary tumor within five years of initial diagnosis Oral Squamous Cell Carcinoma

Intra-oral high-risk locations – Ventro-lateral tongue – Floor of mouth – Soft palate Clinical Staging T1S- Ca-in-situ T1 - Primary <2 cm T2 - Primary between 2-4cm T3 - Primary >4cm T4 - Invasion of contiguous tissue

N0 - No LN mets N1 - One ipsilateral node <3cm N2 - One node >3-6cm or multiple nodes N3 - node >6cm

M0 - no distant metastasis M1 - evidence of distant metastasis Clinical Staging

Stage 5 year survival

Stage I T1N0M0 85% Stage II T2N0M0 66% Stage III T3 or any T w/ N1 41% Stage IV T4 or any T w/ N2 or M1 9% Biopsy of Mucosal Lesions

• Oral cancer • Diagnostic techniques • Biopsy procedure For each mucosal lesion… • Take a good history • Formulate a differential diagnosis • Arrive at a definitive diagnosis Why do I need a differential?

1- Validation 2- Clinical impression may influence diagnostic approach -biopsy vs. alternative technique -incisional vs. excisional biopsy -margins of biopsy -preservation medium 3- Clinical impression may assist pathologist Diagnostic Techniques

• Empiric treatment • Viral cultures • Exfoliative cytology • Biopsy • Adjunctive techniques Cultures

• Primary indications – Herpetic Lesions – Candidiasis? Exfoliative Cytology

• Primary indications – Herpetic lesions – Candidiasis – Oral hairy leukoplakia Biopsy

• Incisional vs. Excisional • Preservation • Site Selection Special Staining

• Histochemistry • Immunohistochemistry • Immunofluorescence Adjunctive Techniques

• Cytology • Vital staining • Light-based • Fluorescence-based Adjunctive Techniques

• “Overall, there is insufficient evidence to support or refute the use of visually based examination adjuncts” • “None of the tests evaluated in this review … can be recommended as a replacement for the currently used standard of a scalpel biopsy and histological assessment.”

Patton LL, Epstein JB, Kerr AR. Adjunctive techniques for oral cancer examination and lesion diagnosis: a systematic review of the literature. J Am Dent Assoc. 2008 Jul;139(7):896-905; quiz 993- 4. Review.

Macey R, Walsh T, Brocklehurst P, Kerr AR, Liu JL, Lingen MW, Ogden GR, Warnakulasuriya S, Scully C. Diagnostic tests for oral cancer and potentially malignant disorders in patients presenting with clinically evident lesions. Cochrane Database Syst Rev. 2015 May 29;5: Adjunctive Techniques

• Clinical considerations –Definition of positive results • Limited to SCCA vs. inclusion of dysplasia –False positives and negatives Nomenclature

• Predictive Values – Refer to likelihood that patients with positive or negative TEST RESULTS have (PPV) or do not have (NPV) disease • Sensitivity and Specificity – Associated with LOW FALSE NEGATIVE and LOW FALSE POSITIVE rates in POPULATIONS TESTED – Of those WITH disease, sensitive tests report most are positive – Of those DISEASE-FREE, specific tests report most are negative Nomenclature

• Screening – Technique applied to patients without signs or symptoms – e.g. mammogram, colonoscopy

• Case-Finding – Technique applied to patients with abnormal signs to confirm a diagnosis – e.g. biopsy, culture Cytology

• OralCDx BrushTest – Introduced in 1999 as Brush Biopsy – Designed for evaluation of clinically- innocuous (class II) lesions – Does NOT provide definitive diagnosis • Results positive, atypical, or negative

• Sensitivity = 91% • Specificity = 91% Tolonium Chloride

• Toluidine Blue – Vital dye designed to stain nucleic acids and abnormal tissues – False positives in reactive lesions – More accurately detects SCCA than dysplasia

• Sensitivity = 81% • Specificity = 70% Light-Based Detection

• Designed for evaluation of cervical lesions • Removes debris and dehydrates cells to better visualize nuclei • Normal lesions appear light blue • Abnormal lesions appear “aceto- white” Vizilite+ • Disposable light packet • Tolonium chloride Vizilite Plus, Microlux

• Preferentially detects leukoplakia and may overlook erythroplakia

• Sensitivity = 77-100% • Specificity = 0-28%

Nagi et al. Efficacy of light based detection systems for early detection of oral cancer and oral potentially malignant disorders: Systematic Review. Med Oral Patol Oral Cir Bucal. 2016.

Rashid and Warnakulasuriya, The use of light-bsed (optical) detection systems as adjuncts in the detection of oral cancer and potentially malignant oral disorders: a systematic review. J Oral Pathol Med. 2015. 44:307-328. Narrow Emission Tissue Fluorescence

• VELscope – Normal mucosa emits a pale green color under 400-460nm VELscope

• Unable to distinguish dysplasia from benign inflammatory conditions • No benefit beyond conventional oral exam • Sensitivity = 22-100% • Specificity = 16-100%

McNamara et al. The role of direct visual fluorescent examination (VELscope) in routine screening for potentially malignant oral mucosal lesions. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012. 114:636-643.

Nagi et al. Efficacy of light based detection systems for early detection of oral cancer and oral potentially malignant disorders: Systematic Review. Med Oral Patol Oral Cir Bucal. 2016. Biopsy of Mucosal Lesions

• Oral cancer • Diagnostic techniques • Biopsy procedure Where do I biopsy?

• Mass/nodule • Red areas (erythroplakia) • Non-homogenous white areas • Papillary/verrucous areas

Large and non-homogenous lesions likely need multiple biopsies Where do I NOT biopsy?

Areas to avoid • Ulcers • Thickly keratinized sites Tufts Oral Pathology Services (TOPS)

• Complimentary biopsy kits • Pre-paid FedEx priority overnight mailers • 24-hour turn around time for diagnosis and treatment suggestions How do I manage the visit?

• Informed consent; potential sequelae • Pain, infection, bleeding, swelling, scarring • Biopsy • Hemostasis • Post-operative instructions • Requisition form • Specimen to pathology How do I complete the paperwork?

• Essential data to include • Date of procedure • Clinician name • Patient information • Name (ALSO ON SPECIMEN JAR) • Date of birth • MEDICAL insurance • History and clinical information • Biopsy site • Clinical diagnosis What else can I do to help?

• Provide as much information as possible to the pathologist along with the specimen to aid in the diagnosis • History • Clinical photographs • Radiographs Thank You