ORAL PATH TERM 2 NOTES.docx

ORAL PATH TERM 2 NOTES Salivary Gland Pathologies Review of Salivary Gland Anatomy, Physiology, & Histology Parotid Gland Supplies 25% of saliva but supplies 50% upon stimulation. Serous gland = watery saliva. Largest major gland. Innervation = CN IX (glossopharyngeal nerve) CN VII (facial nerve...

ORAL PATH TERM 2 NOTES Salivary Gland Pathologies Review of Salivary Gland Anatomy, Physiology, & Histology Parotid Gland Supplies 25% of saliva but supplies 50% upon stimulation. Serous gland = watery saliva. Largest major gland. Innervation = CN IX (glossopharyngeal nerve) CN VII (facial nerve) crosses through the gland, separating the gland in a superficial and deep lobe. Superficial lobe is the more common tumour location. Contains lymph nodes within & around it (drains ear, temporal region, lateral face, eyes). Submandibular Gland Supplies 50-60% of total saliva. Both serous and mucinous acini. Innervation = CN VII (facial nerve). Sublingual Gland Smallest of the major salivary glands. Contains both serous and mucinous acini (mucous cells predominate). Innervation = CN VII (facial nerve). Minor Salivary Glands 600-1000 discrete aggregates of salivary tissue located in the submucosa throughout the oral cavity = labial, lingual, palatal, buccal, glossopalatine, retromolar. Account for 10% of Salivary Flow. Predominantly mucous glands. Exception = Von Ebner’s glands are located around the circumvallate papillae and the folate papillae on the sides of the tongue. Minor glands are NOT found in gingiva, anterior hard palate, and anterior tongue dorsum. Salivary gland pathology does not occur here!!! Salivary Gland Duct System Acini Intercalated ducts (intralobular) Striated Duct (intralobular) Excretory Duct (interlobular) Excretory ducts are 2 cells thick and gradually transition to SSE as they exit the oral cavity. Function of Striated Ducts: Energy is required to fuel electrolyte transportation by cation pumps: Na+ & Cl- are resorbed. K+ & HCO3- are secreted. Secreted saliva is hypotonic. Electrolyte resorption is controlled by autonomic NS and mineralocorticoids (aldosterone) produced by adrenal gland. Myoepithelial Cells Can contract to assist in salivary secretion. May help the acinar cells maintain their polarity. May have some tumour suppressor type activities. Composition of Saliva Water (95%) Electrolytes = Na+, K+, Ck-, HCO3-, Ca2+, Mg2+, HPO2-, SCN-, F- Secretory Proteins = mucins, histatins, cystatin, statherin, peroxidase, lysozyme, lactoferrin, etc. Immunoglobulins = IgA (major), IgG, IgM Etc. (glucose, amino acid, urea, uric acid, lipids, etc.) Salivary Flow Rate Stimulated Whole Saliva (SWS) Normal SWS > 4.5mL in 5 mins. OR 0.9mL/min. Unstimulated Whole Saliva (UWS) Normal UWS > 4.5mL in 15mins. OR 0.2-0.4mL/min. Nervous Control of Salivary Gland Secretion Regulated by reflexes involving the autonomic NS. Unconditioned reflexes Masticatory-Salivary Reflex Sensory inputs from mechanical receptors inside the mouth (located: PDL, muscle, oral mucosa nociceptors). Chewing stimulates salivation. Gustatory-Salivary Reflex Sensory signals from taste-activated receptors in the taste buds. CN VII, IX, and X all play a role in relaying these signals. Conditioned reflexes Associated with higher brain centers. From past positive food experiences, emotional states, depression. ANS & Regulation of Saliva Secretion Parasympathetic branch (main stimulus for salivation) Increase the quantity of saliva. Produces watery, electrolyte, and enzyme rich saliva. Parasympathetic fibers release Ach, which binds to muscarinic cholinergic receptors. Acts on the myoepithelial cells. Increases blood flow to the salivary glands. Sympathetic branch Leads to a lower flow rate than PNS, with more viscous saliva (more mucin). Releases norepinephrine, which binds to alpha-adrenergic receptors. SALIVARY GLAND DISEASES Variations of Normal Asymmetry. Sensitive to Palpation. Traumatic/Reactive Sialolithiasis (sialoliths) Mucocele Ranula Salivary Duct Cyst Injuries (ex: radiation or chemo resulting in gland destruction) Necrotizing sialo metaplasia (trauma related) Infectious Bacterial Acute Bacterial Sialadenitis Viral Acute Viral Parotitis / Mumps HIV Immune Mediated/Systemic Diseases Sjogren Syndrome Ig4 related disease Sarcoidosis Scleroderma Diabetes GVHD Neoplastic Pleomorphic Adenoma Canalicular Adenoma Warthin Tumour Polymorphous Adenocarcinoma Adenoid Cystic Carcinoma Mucoepidermoid Carcinoma Developmental Conditions? VARIATIONS OF NORMAL Salivary glands are often asymmetrical: Palpation of the submandibular glands often reveals two distinctly different sized glands. Significant interpatient variability in the degree of palpable nodularity in the minor salivary glands (particularly in the lower labial mucosa). Bumps in the lower labial mucosa = minor salivary glands. Salivary glands have feelings too… Salivary glands can be sensitive to palpation even in the absence of disease. TRAUMATIC/REACTIVE Sialalithiasis (Sialoliths) = “Salivary Stones” Definition Blockage of the salivary duct by a calcified structure. May be accompanied by acute/chronic sialadenitis depending on the degree of blockage of the duct. Etiology Deposition of calcium salts from the saliva on debris in the duct (such as mucous, bacteria, dead keratinocytes). Clinical Presentation Most occur in submandibular gland duct. Seldom in minor glands, but if present more common in upper lip and buccal mucosa. Episodic pain and swelling of the gland. Especially during meals from back pressure from the saliva. Gland may become secondary infected. Sessile yellow mass. Firm to bony hard. Often located near duct opening, although can be anywhere along the duct. Varying degrees of radiopacity. Sialoliths may occur in the gland itself. Ex: microliths in the parotid gland. Ex: sialoliths in submandibular gland. Case = Pt presents with Hx of pain in right posterior Md which increases during eating. Sialoliths in submandibular gland duct may be mistaken for a dense bony island (idiopathic osteosclerosis). Occlusal radiographs can help with diagnosis. Management Confirm your diagnosis with radiographs. If duct is patent and sialolith is small, can try gentle massage of the gland to get it out. Moist heat, increased water consumption may promote passage of the stone. Many of them will come out by themselves. Surgical retrieval of the stone, possible loss of entire gland. Refer to oral surgeon if it persists, causing pain, large, etc. Sialoendoscopy and lithotripsy also available, although not in NS. Mucocele Definition Ruptured salivary duct spills saliva into the tissues. Etiology Trauma to a minor salivary gland. (Lip biting). Epidemiology All ages, although more common in younger people. Clinical Presentation Most occur in the lower lip mucosa. Tend not to occur in the palate and upper lip. Often asymptomatic. Smooth, dome-shaped nodular swelling. Translucent or blue or pink. History of fluctuation in size!! (unlike salivary gland tumour or fibroma) Macrophages (muciphages) resorb mucus and then the gland produces more mucus, so the lesion “inflates” and “deflates”. Histopathology Submucosal pool of extravasated (spilled) mucus. No epithelial lining. Not a cyst. Surrounded by granulation tissue. Looks like a cyst. Associated with an inflamed gland. Management Attempts to drain a mucocele rarely works. Self resolution tends to only occur if the gland completely fibroses (ex: all acini replaced with scar tissue). Typically require surgical excision. To avoid recurrence, excision must include the affected gland lobules, and its ruptured duct, which are usually directly under the pool of mucus. Need to take out the salivary glands causing the mucocele = ball of grapes underneath the mucocele. Even with proper surgical excision, recurrence is common due to damage of adjacent ducts! Must send surgical specimen for microscopic evaluation to confirm diagnosis and rule out salivary gland tumour! Ranula = Specialized mucocele arising in the floor of the mouth. Etiology Damaged submandibular duct. Sublingual gland may also have ranula. Clinical Presentation Pooled mucus may cross midline. Enlarged with each meal, then regresses. Often pushes tongue up and forward. May bulge submandibular tissue downward. Plunging Ranula Mucus may drain via fascial planes all the way down to the neck and even into the pericardial area. Congenital Ranula Present at birth. Salivary Duct Cyst Etiology Mucus plug or stone or bacteria. Backup pressure causes dilated duct. Duct lining converts to squamous epithelium. Usually minor salivary glands. Leads to a true cyst lined by epithelium. Clinical Presentation Similar to mucocele with same management. Histopathology Lined by SSNKE (true cyst). Mucocele = pseudocyst lined by granulation tissue. Necrotizing Sialometaplasia Definition & Etiology Uncommon, benign, self-limiting ulcer, most likely from ischemic necrosis of salivary tissue. Epidemiology No gender predilection. Teens and young adults. Smokers are predisposed. Posterior hard palate (75% of cases). Clinical Presentation Hx of a non-ulcerated, painful swelling. Usually unilateral but can present bilaterally. 2-3 weeks after onset, a piece of the necrotic tissue sloughs, leaving a crater-like deep ulcer (roughly 1-5cm in size). Ulcer has minimal erythema in the surrounding mucosa and tends to be less painful. Management Incisional biopsy to rule out possible malignancy (SCC and mucoepidermoid carcinoma). Sufficient sized and deep biopsy is important for diagnosis. Once diagnosis is established no Tx is required, as the lesion will heal without Tx in 5-6 weeks. Changes look similar to squamous cell carcinoma. INFECTIOUS Acute Bacterial Sialadenitis Usually in parotid (bilateral in 25% of cases). Painful edema of cheek, peri-orbital region, neck. Reddened, warm skin over the gland. Purulent exudate from duct when glands massaged. Low grade fever, malaise, trismus. Management Complete a screening panoramic radiograph to ensure no blocked ducts contributing to the issue. Antibiotic therapy. Rehydration of the patient. May involve into a more chronic sialadenitis if ductal obstruction and ductal malformations. Gland removal may be necessary. Acute Viral Parotitis (Mumps) Paramyxovirus infection. Diffuse disease of exocrine glands – most often affecting the salivary glands. Other exocrine glands can be affected = pancreas, ovaries, testes. Transmitted via Urine, saliva, respiratory droplets. Incubation period 16-18 days (range 2-4 weeks) Contagious from 1 day before to 14 days after. HIV Primarily affects the parotid glands. Affects roughly 10% of HIV patients. 60% of those have bilateral disease. Local lymphadenopathy is also present. Diffuse infiltrative lymphocytosis syndrome. Get increase in CD8+ cells into the salivary glands, lacrimal glands, kidneys, muscles, nerves and lungs. May be associated with lymphoepithelial cysts. IMMUNE MEDIATED DISEASES/SYSTEMIC DISEASES Xerostomia with Focus on Sjogren’s Syndrome Definition Xerostomia is an objective loss of saliva causing dryness of the oral mucosa. Subjective xerostomia also exists that refers to the sensation of dry mouth with normal salivary flow. Saliva Function Solvent, changes taste, IgA, Anti-bacterial, Buffers, Re-mineralizes enamel, lubricant for swallowing of food, amylase to start digestion, flows to clean teeth, temperature regulation, production of growth factors and other regulatory peptids. Etiology Developmental Salivary gland agenesis (hypoplasia or aplasia). Local Factors Smoking Heat causes dry tissues. Mouth Breathing Increases evaporation. Nocturnal xerostomia (dry mouth when waking up). Decreased Mastication Ill-fitting dentures, illness causing decreased input to the salivary reflexes. Although blockage in a duct or even a neoplasm within one gland could affect the function of one gland, it typically does cause significant xerostomia. Dehydration Decreased water intake, increased caffeine intake, excessive exercise, diarrhea, humidity. Trauma/iatrogenic Radiation Therapy (head & neck cancer patients) Salivary glands are highly radiosensitive and will not regenerate. The loss of saliva is persistent and irreversible. Serous glands exhibit increased radiosensitivity compared to mucous glands (parotids are particularly affected). See increase viscosity of saliva and lower pH. Radioactive iodine Tx for hyperthyroidism or thyroid carcinoma Medications TCA = tricyclic antidepressants Amitriptyline SSRIs Fluoxetine, paroxetine, citalopram Antipsychotics Antihypertensives Diuretics, Beta blockers, CCBs, ACEi Anticholinergics Antihistamines, Decongestants Sedatives (benzodiazepines) Chemotherapy Polypharmacy (combination of drugs that don’t normally cause xerostomia) Systemic Factors Sjogren’s syndrome and other autoimmune diseases. Diabetes Mellitus (excess water loss associated with polyurination) Diabetes insipidus (excess urination, as well as decreased water reabsorption because of aberration in ADH production or activity) Graft versus host disease HIV infection (increase in fat deposition in parotid gland) Lipomatosis in association with HAART, particularly the protease inhibitors, lymphocytosis syndrome in the parotid gland, parotid cysts from glandular hyperplasia. Sarcoidosis (previously discussed) Amyloidosis Hemachromatosis Clinical Presentation Symptoms Mouth feels dry (pt notices decrease saliva). Drinks frequently (especially at night). Natural decrease in saliva at night is very noticeable. Saliva is thicker/ropier. Difficulty eating and swallowing dry foods. Difficulty with speech. Chronic oral pain/burning. Frictional Secondary to candidiasis – erythematous or pseudomembranous Altered taste/loss of taste. Oral malodour typically due to higher bacterial levels and decrease clearance of foodstuffs. Signs Decrease stimulated and unstimulated saliva. Unstimulated flow is <0.1mL/min. Mucosa appears dry. Absence of saliva in floor of the mouth. Altered texture of saliva – white, foamy, or ropey. Decreased retention of dentures. Non-specific mucositis (inflammation and erythema or mucosa). Increased incidence of trauma from teeth, food, or prosthesis. Fissured, dry, and leathery tongue. Candidiasis (erythematous or pseudomembranous) Angular cheilitis Increased cervical root caries and recurrent caries along old restorations. Assessment of the Xerostomic Patient Interview patient for symptoms. Look for clinical signs of xerostomia. Attempt to milk ducts to access quality and quantity of saliva – clear or cloudy, or completely absent. Rule out other underlying illness with thorough review of medial history. Evaluation of stimulated and unstimulated salivary flow can be considered. Management Identify and eliminate the cause (if possible). Increase water intake to 2-3L per day. Eliminate caffeine from diet. Humidify their bedrooms. Implement a caries prevention program. Salivary substitutes. Avoid minty/cinnamon flavoured toothpaste. Avoid alcohol containing mouthrinses. Pharmacological management (Sialogogues) Pilocarpine (Salagen) Parasympathetic agent that can promote saliva secretion by stimulation muscarinic receptors. Cost = $160 for 90 tablets. Prescription Rx: Pilocarpine 5mg tabs Disp: 100 tabs Sig: Take 1 tablet po up to 3 times per day. Pharmacodynamics (stimulated all parasympathetic actions) Increases secretion by all exocrine glands (sweat, salivary, lacrimal, gastric, pancreatic, intestinal, mucous cells of respiratory tract). Smooth muscle stimulation of the intestinal tract may cause increased tone, increased motility, spasm, and tenesmus. Bronchial smooth muscle tone may increase. The tone and motility of urinary tract, gallbladder, and biliary duct smooth muscle may be enhanced. May have paradoxical effects on the CV system. Expected effect of a muscarinic agonist is vasodepression (vasodilation), but administration of pilocarpine may produce HTN after a brief episode of hypotension. Bradycardia and tachycardia have both been reported. Side Effects (gives hot flash-like effects) Chills, cough, diarrhea, warmth, fever, flushing/redness of the skin of face and neck, Increase need to urinate, indigestion, joint pain, nausea, runny nose, tiredness, weakness, sweating. Less common = tachycardia, headache, edema, trembling, trouble swallowing, trouble seeing, vomiting, voice change, etc. Contraindications Narrow angle glaucoma, beta blockers (drug interactions), uncontrolled asthma, cystic fibrosis. Bc of more bronchial secretions Caution in CVD, pulmonary diseases, cholecystitis (gallbladder issues), nephrolithiasis (kidney stones), cognitive/psychiatric problems. Diet Modification Keep high sugar containing foods for mealtime when salivary flow is highest. Avoid spicy and acidic foods. Use milk to help with lubrication of the mouth during mastication. Coconut oil (“Oil Pulling”) Swish for 0.5tbsp for 10 minutes (spit out or swallow) for tissue hydration. Also can help prevent candidiasis. Coconut oil rinse Available at superstore. Night-time Moisturizers Xylimelts ($20 for 40 discs) Use 2 discs nightly or daily. Helps reduce caries. May stimulate some salivation. Saliva Sure ($16 for 90 tabs on amazon) Easy to carry. Pleasant taste No drug interactions or adverse effects Does not require a lot of saliva to dissolve. Biotene Salivary Substitutes Gel or spray Only lubricates the mouth, but coconut oil is better. Caries Prevention Programs Avoid Sugary candies and beverages. Frequent professional visits and prophylaxis are important. High fluoridated toothpastes. Prevident Clinpro 5000 Squigle Enamel Saver Good if can’t tolerate the other toothpastes (soothing to tissues). Application of fluoride varnishes in office. Home fluoride treatment for patient with increased caries rate or severe xerostomia (ex: cancer patients): Neutral NaF gel 1.0% or Prevident (Colgate) 1.1% neutral NaF or Clinpro 5000 1.1% NaF Dispense: 24mL Sig: Place 1 drop per tooth in custom tray, apply 5 minutes daily. Avoid rinsing/eating for 30 mins after Tx. Combine all of these things! High fluoride toothpaste 1X/day + frequent fluoride varnish application + recalls + NaF in custom trays + avoid sugar. Sjogren’s Syndrome Definition Autoimmune disease that involves the salivary and lacrimal glands. Often associated with other systemic diseases such as: Rheumatoid arthritis, SLE, primary biliary cirrhosis, fibromyalgia, polymyositis, scleraderma (systemic sclerosis), vasculitis. Pathogenesis Autoimmune attack on ductal cells of exocrine glands. Salivary glands destroyed and do not regenerate Loss of tolerance in CD4+ T-cells. Characterized by the following autoantibodies: RF RNP (anti ribonucleoprotein) SSA (anti-Ro) & SSB (anti-La) ANA (antinuclear antibodies) Epidemiology 2-3% of adult population. More than 90% are women. Usually occurs at 30-40yrs old. Clinical Presentation Extraoral Keratoconjunctivitis and eye dryness. Erythema and edema. Parotid gland hypertrophy may be present. Associated with an odd lymphoid enlargement with destruction of salivary glands and squamous metaplasia of ducts, called lymphoepithelial lesions. Considered premalignant for lymphoma. Angular cheilitis as well as intraoral candidiasis are also often present (especially median rhomboid glossitis). Intraoral Dysgeusia (taste dysfunction) Tongue depapillation. Dysphagia (often need water to help with eating) Increased caries rate (class Vs) Glossodynia (burning tongue) – often secondary to candidiasis. Diagnostic Criteria 5 items Positive ANA, or SSA, or SSB (blood test) (scores 3) Positive salivary gland biopsy (scores 3) Abnormal ocular staining (scores 1) Schirmer test (scores 1) Low salivary rate UWS (scores 1) Any patient with dry eyes and dry mouth and a score of >4 meet the criteria for Sjogrens Syndrome. Extraglandular conditions that may present in conjunction with Sjogren’s Extra glandular non-visceral systemic manifestations: Joint and muscle pain. Skin. Other visceral symptoms Interstitial pneumonitis Pericarditis Lymphomas Can also see sensory neuropathies – often symmetrical – trigeminal nerve involvement can produce slowly progressing, unilateral, or bilateral facial numbness or para-esthesia, and occasionally painful. Treatment Eyes Artificial tears. Topicla cyclosporin Topical steroids Lid scrubs. Placement of lacrimal punctuate plugs to reduce the clearance of any lacrimal fluid into the nose. Oral (imp) Xerostomia strategies Coconut oil rinses. Pilocarpine (sialogogues) not the best. Watch for signs of candidiasis. Diet modification. If oral stomatitis (burning mouth) is present Benadryl + Maalox + nystatin Topical steroid for acute sores Food grade aloe vera gel rinse and swallow for sores Long Term Prognosis Patients are at risk of progression of lymphoma (5%) Most common type being MALT lymphoma. Risk is about 40X higher than general population, and even greater if the patient has chronic parotid gland enlargement. Sialadenosis Definition Uncommon, non-inflammatory hypertrophy of the salivary glands. Usually the parotid gland. Clinical Presentation Diffuse, slow enlargement of parotid glands. Could be confused with Sjogren’s Syndrome or acute viral parotitis due to mumps. Etiology Disruption of the autonomic nerve supply to the acini causing an aberration secretion and subsequent enlargement of the acini. Associated with: Endocrine disturbances Hypothyroidism Diabetes Mellitus / Diabetes Insipidus Acromegaly Pregnancy Nutritional Deficiencies Alcoholics Bulimia/Anorexia General Malnutrition Medications Antihypertensive Psychotropic drugs Sympathomimetic Drugs Management Treatment of the underlying systemic issue may be required. Referral to family doctor for assessment if not already diagnosed. If a cosmetic concern, can consider partial parotidectomy. In the case of bulimia, a short course of pilocarpine has been shown to be effective. NEOPLASTIC DISEASES Salivary Gland Neoplasms (focus on clinical presentation, not histological) Adenoma = benign / adenocarcinoma = malignant. Both the epithelial and myoepithelial components of salivary glands can undergo benign or malignant transformation. Causes unknown. Prevalence 6/100,000 people per year. Most common neoplasm = benign mixed tumour (pleomorphic adenoma). Most common malignancy = mucoepidermoid carcinoma. Most common site = parotid gland. Most common intra-oral site = hard palate. General rule = larger gland = smaller % of neoplasms that are malignant Minor Salivary Gland Neoplasms Hard/soft palate junction is the most common site. 2nd most common site = upper lip. We rarely have conditions in the upper lip, so if you see something, think about salivary gland neoplasm. Mucoepidermoid is the most common malignancy. Clinical Presentation Asymptomatic submucosal mass, moderately firm. Can’t usually distinguish benign from malignant tumours clinically, but the following signs favor malignant. Hx of rapid growth. Spontaneous ulceration Paresthesia (if in parotid gland) Burning, tingling, numbness Telangiectasias on the surface of mucosa Obvious blood vessels. Histologic Subtypes Benign Pleomorphic adenoma Myoepithelioma Canlicular Adenoma Warthin Tumour (Papillary Cystadenoma lymphomatosum) Malignant Acinic cell carcinoma Adenoid cystic carcinoma Carcinoma ex pleomorphic adenoma (malignant mixed tumour) Clear cell adenocarcinoma Lymphoepithelial carcinoma Mucoepidermoid carcinoma Polymorphous adenocarcinoma Salivary duct carcinoma Minor salivary gland neoplasms presentation based on location. Upper lip Pleomorphic adenoma (PA) Canalicular adenoma (may be multifocal) – 75% occur in upper lip. Cystadenoma (rare and fairly exclusive to minor glands) Polymorphous adenocarcinoma (typically low grade) Salivary duct adenocarcinoma (rare and deadly) Hard palate = most common intraoral site of salivary gland tumours Pleomorphic adenoma (most common site) Mucoepidermoid carcinoma (most common site) Adenoid cystic carcinoma Polymorphous adenocarcinoma (exclusive to minor glands) Lower lip Rare, usually a mucocele or fibroma. Buccal mucosa Pleomorphic adenoma Polymorphous adenocarcinoma Cystadenoma Retromolar pad Mucoepidermoid carcinoma Pleomorphic adenoma Floor of mouth Mucoepidermoid carcinoma Pleomorphic adenoma Pleomorphic Adenoma Most common benign and overall salivary gland neoplasm. A biphasic tumour being composed of both ductal and myoepithelial elements. Clinical Presentation Painless, slow growing firm mass. Present months to years. Any age – predilection for young and middle-aged adults. 30-60yrs (average age 46) Most common primary tumour of childhood. Slight female predilection. Mostly in superficial lobe when in parotid gland. Nerve palsy and pain are rare. Most common intraoral site. Palate > upper lip > buccal mucosa. Only 10% develop in the deep lobe of the parotid gland. Presents as a dumbbell-shaped lesion that appears as a mass of the laryngeal wall and/or soft palate. Treatment Surgical excision with or without total gland removal. Submandibular lesions, minor glands are treated with total gland removal. Good prognosis with cure rate = 95%. Recurrence is higher in parotid gland. Low risk of malignant transformation (3-4%) Carcinoma ex pleomorphic adenoma. Sudden rapid growth Recurrence 90% 5-year survival Treatment Wide excision, often with cervical node dissection and radiotherapy. Canalicular Adenoma Definition Uncommon tumour almost exclusive to the minor salivary glands. Striking predilection for the upper lip (75%) > buccal mucosa Usually in older adult females. May have slight blue hue mimicking a mucocele in upper lip. Rare to see mucocele in upper lip. May be multifocal. Treatment Local surgical excision. Recurrence is uncommon and may simply represent a multifocal presentation. Warthin Tumour Benign parotid tumour (rare in any other salivary gland) 6th to 7th decade – slowly growing mass. Occasionally occur bilaterally (5-17%) Smoking is an associated risk factor (8X). Much lower incidence in black people. Male predilection, although this demographic is changing. Treatment Surgical excision Prognosis: 90-95% cure rate. 5-10% recurrence rate. Overall excellent prognosis Malignant transformation exceptionally rare. Polymorphous Adenocarcinoma Monophasic tumour arising from terminal duct cells. Tends to be low grade malignancy. Almost exclusively to the minor salivary glands. Most common on the hard palate (60%). Older adults – average age 59. Female – 2/3rds May invade the underlying bone. Treatment Low grade neoplasm Wide local excision Metastasis to lymph nodes in 10% of patients, with greater risk in tongue lesions. Long-term follow up. May recur, although often not fatal. NOTE = presence of perineural invasion does not affect prognosis. Adenoid Cystic Carcinoma Pain, increasing dull ache common, often early even before the nodule appears. Bone destruction may be noted. Treatment Wide radical surgical excision and post-radiation treatment even without known residual disease. Chemotherapy is usually reserved for extensive disease and is mainly palliative. Local node mets are uncommon, thus neck dissection is not done. Tendency for persistent and relentless growth. May invade skull, late metastasis (lungs and bones) and cause eventual death. Better prognosis if lower histological grade. Prognosis Grading I = cribriform and tubular pattern II = <30% is solid III = >30% is solid 5-year survival = 60-70% 10-year survival = 50% 20-year survival (grade I and II) = 25% 15-year survival (grade III) = 5% Mucoepidermoid Carcinoma Most common salivary gland malignancy. Parotid is most common site, followed by the palate. Age = 2nd to 7th decade (most common intraoral malignancy of children). Presents intraosseous. Treatment Surgical resection, with more extensive surgery for larger tumours. Neck dissection if clinical indication. Radiation for high grade/stage tumours. Prognosis Depends on grade and stage. 2 grading systems that take into account the extent of cyst formation, the degree of cytologic atypia, the number of mitosis, the presence of necrosis, presence of perineural, lymphovascular invasion, bone invasion. In general, low grade tumours have a high cystic component with a higher proportion of mucous cells. Lower grade tumours have a generally good px with 90-98% being cured with local excision. High grade have 3050% overall survival. Submandibular tumours have worse prognosis. Hard Tissue Pathologies HARD TISSUE/BONE PATHOLOGIES Variation of Normal Stafne Defect Tori Bony Exostoses Traumatic/Reactive Reactive Buccal/Palatal Exostoses Anesthetic Necrosis Idiopathic Osteosclerosis (Dense Bony Island) Alveolar Osteitis Simple Bone Cyst (Traumatic Bone Cyst) Aneurysmal Bone Cyst Central Giant Cell Granuloma Infectious Osteomyelitis Neoplastic Benign Ossifying fibroma Osteoblastoma Osteoma Cementoblastoma Malignant Osteosarcoma Metastatic Diseases Developmental Conditions Cherubism Cleidocranial Dysostosis Osteogenesis Imperfecta (Brittle Bone Disease) Fibrous Dysplasia Cemento-Osseous Dysplasia Paget’s Disease Hypercementosis Acromegaly and Gigantism Gardner Syndrome Developmental Odontogenic Cysts Langerhans Cell Histiocytosis MRONJ (reading) VARIATIONS OF NORMAL Stafne Defect Lingual Concavity of the mandible. Well demarcated radiolucency below inferior alveolar canal; sclerotic border equivalent to the cortex of the mandible. Usually posterior mandible. Etiology Pressure from submandible gland possibly? 3/1000 in adults (rare in children). Male predilection (9:1) Torus Palatinus (Palatal Torus) Definition Bony nodule on the palate likely a developmental anomaly potentially related to occlusal stress. Composed of mature and lamellar bone. Etiology 20/1000 adults. Uncommon in children/teens. More common in Asians and Innuits. Clinical Presentation Flat, spindled, nodular, or lobular. Always at the midline. Typically, <2cm. Asymptomatic Hard. May be seen on panoramic radiograph. Biological Behaviour Starts in early 20s/late teens and enlarges over time. May stop enlarging at any time (rarely diminishes in size). May become nodular/lobular. Overlying mucosa is very thin. No malignant potential. No systemic problems, syndromes. Treatment No Tx needed. Surgical removal only if needed (tend not to recur). Ex: to make dentures. Torus Mandibularis (Mandibular Tori) Definition Acquired cortical nodule with genetic predisposition. Etiology From torque secondary to clenching? Clinical Presentation Lingual of mandible 9/1000 adults. Males = Females More common in Asians 90% bilateral Asymptomatic, unless traumatized. Biological Behaviour Slowly enlarge over time. Large ones = kissing tori, touch in midline, ulcerate. May cause periodontitis from food impaction. Susceptible to MRONJ. Treatment No Tx. Surgical excision for denture or if painful. (Can recur) TRAUMATIC/REACTIVE Bony Exostoses Etiology Developmental anomaly? Response to bruxism? Common 10/1000 adults Uncommon in children/teens. Clinical Presentation Sessile, bony masses Facial of alveolar bone Especially posterior Over root region Palatal of tuberosity Asymptomatic Usually, bilateral. Biologic Behaviour Slowly enlarge for years. Large lesions: possible cause of periodontal problem. Treatment None, except for esthetics, periodontal issues, dentures. Conservative surgical removal. Minimal recurrence. Subpontic Osseous Hyperplasia (Variant of bony exostosis) Rare bony mass under pontic of an FPD. Etiology = chronic irritation/stress from abutment teeth? Takes years to develop. Usually, asymptomatic. Does not disappear when bridge is removed. Treatment = conservative surgical removal. Slight chance of recurrence. Bony Exostoses and tori are prone to trauma and ulceration. May see hyperkeratosis of the traumatic ulceration on the surface. No treatment needed other than routine ulcer care. Expect delayed healing (4-6 weeks). Surgical removal only if needed. Tend not to recur. Oral Ulceration with Bone Sequestra (secondary to alveolar necrosis of the bone) Oral ulcerations may be present for weeks/months. Management Chlorhexidine Gluconate Rinse (Peridex) Swish 15mL for 30s then expectorate in morning & night. Do not touch bone sequestrum unless it is mobile. Anesthetic Necrosis Develops several days after the procedure. Hard palate is most common site. Ranges from shallow to deep irregular ulceration. Etiology: likely due to tissue ischemia from the local anesthetic. No treatment required. Idiopathic Osteosclerosis (Dense Bony Island) Definition Non-expansile radiopaque alteration of trabecular bone, without any association with inflammatory, dysplasia, or neoplastic processes. Epidemiology Found in 5% of people. Common in posterior mandible. May have a slight increased frequency in Asian and African descent. Most commonly arise in first and second decade. Clinical/Radiographic Presentation 0.2-2cm. Variable in shape. Often associated with or in the vicinity of the roots of teeth. No radiolucent rim. Homogenous radiopacity. No effect on adjacent struction. No expansion. Treatment = NONE. Alveolar Osteitis (Dry Socket) Definition Premature fibrinolysis of the initial fibrin clot. Etiology Smokers because heat and lack of blood supply causes clot to die. Clinical Presentation More prevalent in the mandible (especially mandibular 3rd molars). Often see a gray clot (dead) and exposed bone that is VERY sensitive to probing. Typically starts 3-4 days after extraction. Painful. May be foul smelling and may have associated lymphadenopathy. Treatment Irrigate socket to ensure no food debris, root tips, etc. Eugenol paste (ZOE) with gauze changed every 24hrs for 3 days, then every 2-3 days until patient is pain free. Analgesics. Resolves by itself. Simple Bone Cyst (Traumatic Bone Cyst) Definition A simple bone cyst is a cavity that develops within the bone, that is benign, empty, or fluid containing, but no epithelial lining. May be related to trauma. Epidemiology Incidental finding – mostly in young individuals between the age of 10-20 years. Would be rare to see over the age of 35 years. Slight male predilection. Clinical Presentation Occur in any bone in the body. In the gnathic bones – marked predilection for the mandible. May be asymptomatic or present as a bony swelling. Well delineated radiolucency with thin cortex – usually unilocular but can become multilocular if large. 1-10cm. Dome-like projections that scallop between the teeth. Root resorption, loss of lamina dura is not common. May see in association with other bone disorders (osseous-dysplasia, fibro-osseous lesions). Management Simple Surgical exploration and curettage. Usually, normal radiographic findings are present after 12-17 months. Low recurrence rate. Aneurysmal Bone Cyst Definition Intraosseous accumulation of variable-sized, blood-filled spaces in a background of fibrous tissue and reactive bone. It is basically an aneurysm inside the bone. 20-30% form in association with other lesions (most commonly fibro-osseous lesions or central giant cell granulomas). De novo or primary ABCs may be related to USP6 (TRE17) oncogene upregulation. Clinicla Features Primarily in long bones (only 2% arise in gnathic location). Most commonly in younger patients – peak in second decade. Predilection for the posterior mandible. Most common presentation: rapidly enlarging bony swelling – may displace teeth. Radiographic Appearance Unlilocular to multilocular radiolucency. Well or poorly defined. “Punched out appearance” Histopathology Blood filled spaces that lack endothelial/epithelial lining. Surrounded by fibrous tissue with multinucleated giant cells. Treatment Curettage or enucleation. Looks like a blood-soaked sponge. En bloc resection for extensive or recurrent lesions. Most gnathic lesions are low-flow vascularity. Takes 6 months to 1 year for bone to heal. Highly variable recurrence (8-70%). Good long-term prognosis. Central Giant Cell Granuloma Definition Non-neoplastic lesion of the bone that can behave in a non-aggressive or aggressive manner. Etiology = unknown. Epidemiology Occurs in a wide age range, with 60% of the cases in individuals under the age of 30. When present in older people – suspect hyperparathyroidism. Slight female predilection. 70% occur in the mandible (with epicenter anterior to 6s = anterior mandible). Histology Identical to brown’s tumours of hyperparathyroidism and peripheral giant cell granuloma and jaw lesions of cherubism. Basically, multinucleated giant cells and blood cells = granuloma. Radiology Minimal to no cortication. Maxillary lesions are very ill-defined (looks like malignancy). Radiolucent with occasional ill-defined wispy septations (represents immature bone formation so they are very granular in appearance). Likes to resorb teeth, will see loss of lamina dura around teeth (compared to simple bone cyst which scallops between roots). Strong propensity for jaw expansion. Treatment Curettage, recurrence 15-20%. Aggressive lesions and those in younger patients are more likely to recur. Recurrent lesions may respond to further curettage, while aggressive lesions may need radical en bloc surgical resection. Prognosis is good, despite recurrence. Alternative medical management Larger aggressive lesions sometimes first need medical tx to stop growth and shrink lesion, then surgery 3 months later when lesion is small enough. Triamcinolone acetonide (steroid) intralesional injections. Calcitonin subcutaneous injection or nasal spray. Interferon alpha (anti-angiogenic agent). Imatinib (protein tyrosine kinase inhibitor = cases a reduction in RANK receptors therefore decreasing osteoclastogenesis) Denosumab (binds to RANKL) Bisphosphonates. DEVELOPMENTAL Cherubsim Definition Developmental anomaly that makes cherubic facies. AD (autosomal dominant) inheritance. Mutation in a gene that affects bone metabolism producing lytic bone comparable to central giant cell granulomas. Epidemiology Males = females Diagnosed usually under 5 years. Rare. Clinical Presentation Usually bilateral, maybe all 4 quadrants. Greatly expansile radiolucency (usually multilocular). Face appears greatly enlarged. “Eyes towards heaven” (sclera seen at bottom) Painless Tooth buds moved, sometimes dramatically. Wide alveolus. Management Enlarges until puberty, then regresses. Face is approaching normalcy by 25-40 years old. No treatment required, unless fracture develops in the site of the granulomas. Cleidocranial Dysostosis Definition Autosomal dominant malformation syndrome associated with a mutation in the RUNX2 (CBFA1) gene on chromosome 6p. RUNX2 guides normal osteoblastic bone differentiation and appropriate bone formation (master gene). May play a role in tooth development. 1/1,000,000 births. Variable expressibility and almost complete penetrance. May have shorter stature. Primarily affects the skull, clavicles, and dentition. Skull Hypoplasia of maxilla. Brachycephaly of the skull (reduced A-P dimension and increased width). Small face relative to cranium. Open skull sutures and multiple Wormian bones within the sutures. Frontal and parietal bossing. Broad nose – saddle nose – missing nasal bone. Hypertelorism. Possible hearing conduction problems if eustachian tubes are underdeveloped. Other bones may be affected other than clavicles: long bones, vertebrae, pelvis, hands, and feet (short/tapered). Clavicles Complete absence or aplasia of the clavicles. Can move shoulder girdle excessively. Oral Cavity Presentation Underdeveloped maxilla with thin zygomatic arch. Underdeveloped paranasal sinuses (maxillary sinuses may be absent). Narrow and high palatal vault may be present. Normal size mandible. May see an open mandibular symphysis. Mandibular prognathism develops with age. Underdeveloped coronoid processes (thin and pointy). Unerupted and supernumerary teeth (up to 60 teeth). The unerupted teeth may be associated with dentigerous cyst. Retained primary teeth. Ectopic teeth. Crown and root abnormalities. Treatment Most patients function well. Major problems are dental implications. Many surgeries, including exposure of teeth and forced eruption orthodontically. Helps to prevent mandibular prognathism. Extractions of supernumerary teeth when needed. Orthognathic surgery. Osteogenesis Imperfecta (brittle bone disease) Definition Osteogenesis imperfecta is an inheritable bone disease associated with a defect in COL1A1 (chromosome 17) or COL1A2 (chromosome 7) resulting in impairment in collagen maturation. There is a failure of bone to mature – maintenance of woven bone. 4 presentation types (I, II, III, IV) Many sporadic cases are also reported. 1/18,000 births Male = Female Clinical Presentation Short stature Bowing of legs, arms Deformity of long bones Pathologic fracture Irregular mosaic skull = Wormian skull Hypermobile joints Capillary fragility Pathologic bleeds Osteopenia (decrease in bone density) Hearing deficits Blue sclera Oral Presentation Maxillary hypoplasia, malocclusion. Rare = radiolucent/opaque areas of jaws. Teeth: Blue/gray “translucent teeth Opalescent teeth Like dentinogenesis imperfecta Both dentitions affected Small or obliterated pulp chamber Maybe shell teeth (especially primary teeth) Fracture of crowns/enamel. OA Types Type I = Most common Mildest form. 10% have fractures at birth. Blue sclera Hearing loss <30years old Opalescent teeth AD inheritance. Type II Most severe (90% stillborn or die <4weeks) AD or AR inheritance. Type III Second most severe form. Usually noticed after 6 months. Sclera and teeth often normal. Most die before adulthood. From cardiopulmonary conditions. Kyphoscoliosis AD or AR inheritance. Type IV Fractures in 50% at birth. Blue sclera usually fades with time. AD inheritance. Treatment/Prognosis Risk of broken bones. Cautious living. C-section for birth. IV/oral bisphosphonates. Anemia (less marrow space therefore less hematopoietic tissue making RBCs) Enamel fractures off (weak dentin) Requires extensive dentistry. Avoid implants. Orthodontics can be considered. Benign Fibro-osseous lesions Diverse group of processes characterized by replacement of normal bone with fibrous tissue and abnormal bone deposition. Includes developmental lesions, dysplastic processes and neoplasms. Cemento-osseous dysplasia (periapical, focal, florid). Fibrous Dysplasia Ossifying fibroma (benign tumour) Clinical, radiographic, and histologic correlation needed for diagnosis. Fibrous Dysplasia Definition An acquired condition that results in a localized change in bone metabolism. Replacement of normal bone with fibrous tissue + varying amounts of abnormal-appearing bone. Strange shaped bony trabeculae with few osteoblasts rimming the bone. This abnormal bone will fuse into surrounding normal bone. Etiology Associated with a post-zygotic mutation in the GNAS 1 gene. Depending on the time of the mutation dictates how many different cells will be affected. Epidemiology Males = Females 7-20 years of age. Jaws = most common sites (predilection for maxilla). Clinical Presentation Painless slow bony enlargement. Enlargement is quite diffuse often following the contours of the bone. Radiographic Appearance Ill-defined with gradually blending borders. Important feature to set apart from other bone lesions. Ground glass appearance to the bone. Lamina dure of teeth is faint or lost as it blends in with the atypical bone with loss of the PDL space. Teeth will remain vital. Cortical bone will be thinned. May also see a mixture of radiolucent and radiopaque bone with granular bone pattern or peau d’orange appearance. May see a swirling bone pattern reminiscent of a fingerprint. Early stages = may be more radiolucent. Cotton wool appearance. Bone expansion with thinning of the cortex – tends to follow/maintain bony contours. Obliteration of the sinus in maxillary lesions. Tends to displace the IAN canal. Tends to not resorb teeth, although may cause displacement. Mandibular Involvement Occlusal view Clear delineation between expanded lesional bone and uninvolved soft tissue. Polyostotic Presentation Typically diagnosed by age 10. Slight female predilection. Typically involve the craniofacial skeleton, pelvic bones and femur. 87% of polyostotic cases will have craniofacial involvement. Small subset will develop syndromic presentation. Pain and pathologic fracture in the long bones. Bowing deformity of the legs. Malocclusions, facial asymmetry, vision and hearing problems. McCune Albright Syndrome When the melanocytes are affected. Café au lait spots. Occur on the skin most commonly trunk and thighs (unilateral). Present at birth or shortly after. Irregular margins Recall neurofibromatosis type 1 has café au lait spots with much smoother edges. Café au lait oral lesions may also occur. Develop in early adulthood and progress with age. Recall = Oral melanotic macule (no malignant potential) Focal pigmentation usually less than 7mm. Normal number of melanocytes but increased melanin in basal keratinocytes. Broad age range – most common in 40’s and in women. Most common site is the lower lip vermillion. Rare to see in children. Recall = Hereditary Intestinal Polyposis (Peutz-Jeghers) Syndrome Multiple periorificial / buccal mucosae, tongue +/- fingers/toes 1-12mm brown-blue-black macules. Typically start to show up in infants. 90% of cases will have oral involvement. Skin macules will not wax and wane with sun like ephelis (freckles). Pigment fades at puberty with the exception of the buccal mucosa. When the endocrine cells are affected: Typically, multiple endocrinopathies. Sexual precocity (very early puberty) = most common. Females menstruate at 9yrs old. Breast development and pubic hair at age 4. Hyperthyroidism. Hyperparathyroidism. Management of Fibrous Dysplasia Lesions tend to stabilize and stop enlarging when skeletal maturation is complete. Small lesions can be surgically resected. Diffuse nature and large size of some lesions precludes removal without extensive surgery. Surgery is usually for cosmetic reasons. Regrowth seen in 25-50% of patients. Heal well after dental extractions. May be treated with bisphosphonates or Denosumab. Denosumab = monoclonal antibody that inhibits osteoclast formation by preventing the interaction of RANKL (ligand) with RANK receptor. Malignant change very rare. Usually associated with patients who received radiation therapy. Cemento-Osseous Dysplasia Benign fibro-osseous lesions occur in the tooth bearing areas of the jaws. Most common fibro-osseous lesion encountered in clinical practice. Possible arising from the PDL or represents a defect in bone remodeling triggered by trauma or underlying hormonal imbalance. 3 forms = Periapical, Focal, Florid. Radiology of Osseous Dysplasia All 3 forms progress through similar stages: Starts radiolucent with variable amount of cortication and eventual loss of lamina dura around the tooth. Gradually increase in opacity from inside out, with the radiopaque presentation still having a radiolucent rim. Lesions usually are less than 1-1.5cm in size. Periapical Cemento-Osseous Dysplasia Most common Multifocal. Usually periapical to mandibular anterior teeth. Marked female predilection (10-14:1). 70% black people. Adults typically (we do not see this under 20yrs old). “End Stage” mature lesion is fully radiopaque with radiolucent rim. Underlying tooth is intact. Most diagnosed without biopsy. Treatment None (no symptoms, no expansion). Focal Cemento-Osseous Dysplasia Uncommon, solitary, usually periapical to a mandibular molar. 90% are females (many in caucasians). Usually <1.5cm. Asymptomatic. No cortical expansion. Gradually increasing radiopacity. Treatment NONE. Monitor. Florid Cemento-Osseous Dysplasia Appears with multifocal involvement not limited to the anterior mandible. Predominantly involves women of african descent (more than 90% according to some case series) with a predilection for middle-aged to older adults. Intermediate frequency among east asian populations. In some cases, the patient may complain of dull pain. Prone to infection: an alveolar sinus tract may be present, exposing yellowish, avascular bone to the oral cavity – usually under a denture. Although rare, some degree of expansion may be noted in involved areas. May also be associated with simple bone cysts. Histology of Osseous Dysplasia (All three patterns have similar histology) Fragments of cellular mesenchymal tissue composed of fibroblasts and collagen fibers. Numerous small blood vessels. Mixture of woven bone, lamellar bone and cementum-like particles. With maturation the trabeculae of bone will get thicker and look like ginger root. Management Most cases of PCD and florid COD have distinctive clinical and radiographic features and do not require a biopsy for diagnosis. Focal cemento-osseous dysplasia has less specific clinical/radiographic features and biopsy may be necessary. Once lesions become sclerotic, they are hypovascular and prone to necrosis – want to avoid any treatment if possible. Very rare reports of malignant transformation. Paget’s Disease of Bone (Osteitis Deformans) Definition Paget’s disease of bone is a condition characterized by abnormal and disorganized resorption and deposition of bone, resulting in weakening of the affected bones and deformation due to overall net increase in bone deposition. Pathophysiology: Thought to be associated with abnormal osteoclast function. Epidemiology Primary affects British and northern/western Europeans, north americans, Australia, and new zealand. Affects 1-2% of white adults >55yrs but the incidence is on the decline. Would be rare to see under 40years old. Male predilection. 1/3 will have 1st degree relative affected. Clinical Presentation 40% present with bone and joint pain. Lumbar vertebrae, pelvis, skull, and femur most commonly affected. Can be monostotic or polyostotic. Thickened, weak, bowing bones. Simian (monkey-like) posture and gait. Increased skull circumference. “Hat too small”, narrowing of foramina – cranial nerve pain and deafness or visual impairment. Nasal obstruction. Radiology Enlarged cranium, maxilla. Early stages have decreased radiodensity and a coarse trabecular pattern. Overtime evolves to cotton wool appearance. Intraoral Jaw involvement in 17% of patients, with 2:1 predilection for the maxilla. Symmetrical maxillary alveolar enlargement. “CUD too small” or teeth develop open contacts. Lion-like facial deformity. Cotton wool appearance of alveolar bone. Generalized hypercementosis may be present. Diagnosis of Paget’s Disease of Bone Correlation of clinical, radiographic, and laboratory investigations. Histopathologic examination often unnecessary. Lab findings High serum alkaline phosphatase. Must also assess liver enzymes, to exclude elevated alkaline phosphatase of hepatic origin. Normal calcium & phosphorus levels. If alkaline phosphatase is normal; can test. Serum N-terminal propeptide of type 1 collagen as a marker for bone formation. Urinary N-terminal telopeptide of type 1 collagen for bone resorption. Bone Scintigraphy to determine the extent of the disease. When the mandible is affected, the bone scan may demonstrate marked uptake throughout the entire mandible from condyle to condyle, a feature that has been termed black beard or Lincoln’s sign. Treatment Chronic and slowly progressive (seldom causes death). In patients with more limited involvement and no symptoms, no Tx required. Symptomatic or extensive disease will be treated with bisphosphonates (may induce disease remission). Uncertain if bisphosphonates will reduce long term risks of osteoarthritis, bone deformity, and deafness. The goal of therapy is to achieve midrange normal levels of serum alkaline phosphatase, with retreatment occurring when values rise 25% higher than normal. Bone pain often may be controlled by acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs). Long Term Complications Dental complications with extractions: Early stage = jaw hypervascularity = severe bleeding. Later stage = hypovascular = osteomyelitis due to poor healing (especially if taking bisphosphonates). Presece of hypercementosis complicates the extraction. Malignant transformation of pagetoid bone into a sarcoma, with osteosarcoma being the most common – lifetime risk is <1%. Most common in the pelvis or long bones, with the skull and jaw bones being rarely affected. Constant or worsening bone pain, new mass or sudden fracture are worrisome for malignancy. Hypercementosis Definition Excess production of cementum primarily at the apex of the tooth. Non-neoplastic, non-developmental. Etiology Local factors Abnormal occlusal trauma Adjacent inflammation (pulpal, periapical, periodontal) Unopposed teeth (supraeruption) Repair of vital root fracture. Systemic factors Acromegaly and pituitary gigantism Arthritis Paget’s disease of bone Rheumatic fever Thyroid goiter Garnder syndrome Vitamin A deficiency Clinical Presentation Thickened cementum. Often has a thickened PDL around it. Asymptomatic Tooth is vital. Usually mandibular molars. Often multiple teeth involved. Think Paget’s disease if multiple teeth. No cortical expansion. Treatment NONE. RCT and extraction difficult. Medication-Related Osteonecrosis of the Jaw (MRONJ) = Reading Definition Avascular necrosis of the bone. Etiology Associated with the oral and IV use of anti-resorptive medications such as bisphosphonates and RANKL inhibitors, as well as the use of anti-angiogenic medications such as tyrosine kinase inhibitors (TKI) and vascular endothelial growth factor (VEGF) inhibitors. Diagnosis Patients are considered to have MRONJ if all the following 3 criteria are met: Current or previous exposure to anti-resorptive or anti-angiogenic agents. Exposed bone, or bone that can be probed through an extra- or intra-oral fistula for over 8 weeks. No history of radiation therapy to head and neck or obvious metastatic disease. Pathogenesis Inhibition of bone resorption and remodeling. Increased rate of bone remodeling in the jaws may be part of the reason this area is more predisposed to the condition. Infection Increased microbial load in the oral cavity. Inhibition of angiogenesis From anti-angiogenic meds, but also bisphosphonates thus affect healing. Toxicity to other cells Oral epithelial cells have been shown to have increased apoptosis in vitro after exposure to bisphosphonates. Innate or acquired immune dysfunction. Patients are at RISK. Cancer patients taking anti-resorptive medications (typically they are taking IV bisphosphonates such as Zoledronate or the RANKL inhibitor Denosumab). Ex: patients with multiple myeloma and metastatic cancers with bone lesions such as breast cancer, prostate cancer and lung cancer. Incidence is related to the specific drug the patient is taking. Zoledronate (zometa) = 0.7-6.7% with the risk increasing after 2 years of taking the medication. RANKL inhibitor = 0.7-1.9%. Cancer patients taking anti-angiogenic drugs 0.2% Incidence will increase with concurrent anti-resorptive therapy 0.9% Patients taking anti-resorptives for other bone diseases such as paget’s disease or osteogenesis imperfecta or dentinogenesis imperfecta type 1 or for osteopenia and osteoporosis. Incidence: Oral BP (bisphosphonates) = 0.1%, although this risk does double to 0.2% after 4 years. IV BP or RANKL inhibitors = 0.0017-0.04%. Patient’s taking anti-angiogenic medications only: Thought to be quite rare, 59 patients noted in an extensive literature review, 37% were associated with a recent dental extraction. Other Confounding Risk Factors Duration of medication increases the risk. Dento-alveolar surgery – major risk factor (52-61% extraction is precipitating event). Risk factor amongst patients exposed to oral BP undergoing extraction is though to be 0.5%. NOTE: risk associated with other procedures (implants, endo, or perio is unknown). Implants are thought to increase risk, although only contra-indicated in cancer patients taking BP’s. Anatomical location: more prevalent in the mandible. Pre-existing periodontal diseases/periapical infections. Other meds on board: corticosteroids (stimulate bone resorption) Other systemic diseases: anemia, diabetes (affects healing) Radiology Radiographic changes seen only after the significant bone involvement. Early or late changes can mimic apical periodontitis, osteomyelitis, primary or metastatic malignancy. Mottled bone can mimic osteomyelitis. Sometimes widening of PDL space. Usually painful, non-healing, dense, exposed bone precipitated by extractions, perio Tx, surgical endo, denture trauma. May occur spontaneously! Bone Scintigraphy (Bone Scan) Can be used to highlight increased metabolic activity within bone. Staging of MRONJ (guides Tx) At risk patients First identified based on the medical histories noted above and preventive strategies can be implemented. Most important for cancer vs. osteoporosis. Example: cancer patients can undergo rigorous pre-treatment dental exam and Tx of any problem teeth prior to initiating the risk causing medications. Dentures should be evaluated as potential sources of chromic trauma. If possible, any initiation of drug regiments should be post-poned until soft tissue healing has occurred after recent dental extractions. (1 month) (even more ideally would be bony healing). Patient education is also important about minimizing potential risk factor that may predispose them to the developing this condition, which includes poor nutrition, poor oral hygiene practices, smoking, and alcohol use, poorly controlled diabetes, and concurrent glucocorticoid use (systemic or topical). Some investigations have recommended antibiotic prophylaxis for 1 day before the procedure and 3 days post procedure when bone manipulation is absolutely necessary. At risk patients (oral BP specifically) In oral bisphosphonate patients taking the drug over 4 years may benefit for a drug holiday (2-3 months prior and re-initiated after bony healing), although this is controversial. If <4yrs and no other clinical risk factors – all procedures are acceptable. Of note: recent animal studies have demonstrated impaired long-term implant healing. If <4 years, but taking steroids or anti-angiogenic meds: Consider 2 month drug holiday and the anti-angiogenic drugs not re-initiated until bony healing is confirmed. Drug holidays for patients taking denosumab for osteoporosis: there is a rebound increase in bone resorption following discontinuation of DMB, resulting in an increased risk of multi-level vertebral fractures. Therefore, if DMB is to be suspended, the best strategy to minimize risk of MRONJ and risk of rebound fractures is to optimize drug holiday timing: perform dentoalveolar surgery 3-4 months following last dose of DMB, and reinstitute it 6-8 weeks post-surgery. Take home message = contact family doctor for opinion – never instruct a patient to discontinue their anti-resorptive medication without medical input. MRONJ – Stage 0 No exposed bone, but do present with ill-defined symptoms: Bone pain Odontalgia with no dental cause Sinus pain (may see inflammation and thickening in sinus wall) Altered neurosensory function. Tooth mobility without periodontal disease. Radiographic changes: altered trabecular pattern or persistence of an unremodelled socket or areas of osteosclerosis, thickening or obscuring of PDL. Close monitoring is required and possible systemic pain meds. Difficult stage to recognize = easy to mistake changes for periapical infection when at the apex of the tooth. MRONJ – Stage 1 Patients present with exposed bone and necrotic bone or a fistula that probes down to bone with no evidence of any active infection. Localized to the alveolar bone. Management Patients can be treated with anti-microbial rinses (ex: 0.12% CHX gluconate) and monitored closely. Remove any mobile sequestra of bone if present. If disease is progressive, then more aggressive surgical intervention may be considered. MRONJ – Stage 2 Patients present with exposed bone or fistula that probes down to the bone with active infection (same as stage 1). Pain, pus and lymphadenopathy are present. Similar radiographics to stage 0. Treatment Microbial rinses as well as systemic broad spectrum antibiotics including amoxicillin and clavulanic acid and close follow up. Operative therapy to reduce volume of colonized organisms, or removal of necrotic bone may be considered. In fact, more evidence is demonstrating that surgical intervention can be quite successful in patients capable of tolerating surgical intervention. MRONJ – Stage 3 Patients with stage 2 disease, but the extent of the disease has spread: Past the alveolar bone into the border of the ramus, into the sinus floor, and the zygoma. OR a pathologic fracture has occurred. OR an extra-oral fistula. OR a naso-antral-oral fistula. OR the osteolysis extends to the border of the mandible or sinus floor. Treatment With surgical debridement, possible resection and systemic antibiotics. Regardless of the stage of the disease, any exposed and mobile bone fragments should be removed, regardless of the stage of the disease. Extraction of symptomatic (infected) teeth within the diseased site should be considered. Example of MRONJ CASE Clinical Exam Pain and bleeding and pus upon probing, with deep probing depth on distal of 47 in a patient taking IV bisphosphonates for multiple myeloma. Radiographic features are discrete. Could be mistaken for periodontal disease if didn’t consider patient’s medical history. Make sure to screen patient about to undergo cancer therapy and bisphosphonate therapy to avoid need for future extractions. Management of this case (Stage 2 MRONJ) Coarse of broad-spectrum antibiotics (amoxiclav 625mg TID). Effective analgesia. OHI = long-handled angles interdental brushes with CHX gel to help control the infection and inflammation. At her two-week review, the pain and bleeding had reduced and the communication to bone via the periodontium was still present. Elimination of the deep pocket as a continued source of bacteria will likely be required for complete resolution. INFECTIOUS Osteomyelitis Definition An acute or chronic inflammation of bone and marrow. Classic presentation usually from bacterial infection. Staphylococcus aureus Staphylococcus epidermitis Escherichia coli Salmonella (sickle cell disease) Children: usually from blood Adults: usually from bone contact with “outside” Jaws are almost always from dental infections. Mandible >> maxilla Males >> females Clinical Subtypes Bacterial associated osteomyelitis: Acute suppurative osteomyelitis Chronic suppurative osteomyelitis Diffuse sclerosing osteomyelitis Condensing osteitis is an example of a localized presentation of sclerosing osteomyelitis. Idiopathic inflammatory disorders (not common): Chromic non-bacterial osteomyelitis (aka primary chronic osteomyelitis) Resembles diffuse sclerosing osteomyelitis, but there is no obvious bone infection, no suppuration and no sequestra. Condition does not respond to antibiotics. Acute Osteomyelitis Clinical Features Symptoms are of less than one month’s duration. Erythema, edema in overlying skin. Lymphadenitis. Fever, malaise. Pain. Radiographic Ill-defined moth-eaten radiolucency. May see widened PDL. Loss of lamina dura. Sequestrum (dead bone fragment within the lesion). Involucrum (sequestrum covered with new reactive bone). Cortical perforation. Caution: draining fistula may develop. Treatment Antibiotics Amoxicillin, metronidazole, clindamycin. Concurrent bacterial culturing should be done while the patient is taking broad-spectrum antibiotic in case the patient is unresponsive and needs a different specific antibiotic. Surgical removal of damaged bone may be required. Curettage. Block resection. Chronic Suppurative Osteomyelitis Definition Chronic infection that typically evolves from acute osteomyelitis. Body has had time to react. Formation of granulation tissue and scar around the area of infection. Makes it difficult to antibiotics to reach the area. Leads to dead space in the bone acting as a reservoir for more bacteria. Creates a “smouldering” infection that must be aggressively managed. Clinical Presentation (similar to acute osteomyelitis) Swelling Pain (during acute exacerbations) Sinus formation Purulent discharge Sequestrum formation Tooth loss. Pathologic fracture Paresthesia in more advanced cases. Radiographic Ragged irregular radiolucency with central radiopacities. May see periosteum bone reaction with new bone formation. Treatment Surgical intervention is mandatory with the goal of removing all diseased bone. IV antibiotics. Difficult to resolve cases are often associated with hypovascularized bone. Ex: Hx of radiotherapy, Paget’s Disease, Florid Cemento-Osseous Dysplasia. NEOPLASTIC (Benign) (Central) Ossifying Fibroma “Relatively rare” benign neoplasm characterized by fibrous tissue, bone, and cementum-like spicules. Not related to “peripheral ossifying fibroma” Significant growth potential yet tend to remain asymptomatic – present in cranioskeleton primarily but can occur in the long bones (similar entity). Usually presents in younger adults with female predilection. Usually, well-defined, from radiolucent to mixed. Typically, would never be completely radiopaque like a mature PCD or complex odontoma. Radiolucent rim +/- sclerotic border. Strong predilection for mandible – molar and premolar region. Should be able to appreciate concentric growth pattern (i.e., growth in all directions – epicenter typically not centered around tooth apex and is radiopaque). Causes thinning of cortices but does not usually perforate them. Treatment Complete surgical excision with simple enucleation – should separate easily away from the bone (because of the radiolucent rim = fibrous capsule) Important to note at time of surgery as helpful to relay to pathologist to assist in diagnosis. Ex: Compared to fibrous dysplasia that blends into surrounding bone (no fibrous capsule) and does not enucleate easily. Recurrences are uncommon. Larger resection and reconstruction may be required for larger lesions – there are some more aggressive variants that do exist. No evidence that the lesions undergo malignant transformation. Osteoblastoma Definition Benign tumour of osteoblasts that presents with an ill-defined or well-defined radiolucent/radiopaque entity that is typically larger than 2cm and associated with pain – RARE and still presents in people under the age of 30 years. Predilection for extra-gnathic locations. When in the jaws – typically mandible. Osteoma Definition Osteoma is a benign tumour of bone composed of mature compact or cancellous bone that tends to occur exclusively in the craniofacial skeleton. Clinical Rare to occur as a solitary lesion (multiple lesions are associated with Gardner syndrome). Commonly arise in the 2nd to 4th decade of life as an expansile mass. Most gnathic lesions are in the inferior mandible, ramus, or condyle. Well circumscribed radiopacity arising from cortical plate or from endosteal surface of the bone. Has no radiolucent halo. (unlike ossifying fibroma = radiolucent rim) Less radiodense than tooth structure. Unlike complex odontoma. Peripheral Osteoma “Peripheral” = arising from the cortex Example is quite homogenous but may also see examples that are much more reminiscent of a cortex and internal trabeculae of bone as noted below. CASE 18-year-old girl presents with abnormal mouth opening for 8 months. Her medical history revealed a surgery to remove an epidermoid cyst in the knee 4 years ago. She has developed abdominal pain and frequent diarrhea for 18 months. Extra-oral examination showed a fixed nodular swelling in the right side of the mandible (angle region). Intra-oral exam WNL. Radiographic (pan and CT scan) 2 well-defined markedly radiopaque/radiodense lesions arising on the ramus and the mandible angle. Look like 2 osteomas. Colonoscopy showed colonic and rectal polyposis. Biopsy showed multiple tubular adenomas with low grade dysplasia in the GI tract. Final diagnosis = Gardner’s Syndrome. Gardner Syndrome = Familial Adenomatous Polyposis Autosomal dominant inherited disorders with 100% penetrance, and is considered part of a spectrum of familial colorectal polyposis. FAP = 1/10,000; 5% have Gardner Syndrome. Gardner Syndrome presents with colonic manifestations along with a variety of findings associated with the skin, soft tissues, retina, skeletal system, and teeth. Cancer predisposition syndrome. Oral Manifestations (often precede the GI presentation) Supernumerary teeth and impacted teeth (fewer than cleidocranial dysplasia) About 20% of affected patients. Multiple odontomas. Multiple osteomas (3-6 lesions) in 90% of patients. Predilection for frontal bone, sphenoid bone, mandible and maxilla. Mandibular lesions are often at the angle and cause facial deformity. Often precede colonic polyps. Large dense bony islands (enostosis) = idiopathic osteosclerosis NOTE = even if osteomas are not present, the presence of 5 or more dense bone islands should prompt an investigation for Gardner Syndrome. Clinical Presentation Adenomatous intestinal polyposis. High risk of adenocarcinoma (>50% risk) Often undergo prophylactic colonectomy. Epidermoid cysts of skin. Desmoid tumours of skin. Aggressive fibromatosis. Rare: thyroid carcinoma. Rare: pigmented lesions on ocular fundus. Treatment Osteomas = conservative excision. GI polyps = monitored carefully. Removed if too large, too numerous, or prophylactic colectomy. Skin cysts = conservative excision. Fibrous tumours = conservative excision. Cementoblastoma Definition Cementoblastoma is an odontogenic neoplasm of cementoblasts and is thought to be the only tumour associated with cementoblasts. Epidemiology Large age range – predilection for 20-30’s decade (young adults). Shares the identical histopathology to an osteoblastoma but is related to a tooth. Clinical Presentation Fused to a root, with a well-defined radiolucent rim (represents an abnormal PDL). Resorbs the root as it grows. 50% of cases involve the lower 6’s. May be locally aggressive. Usually no larger than 1-2cm, although a gigantiform variant exists. May be painful, in some cases can cause local expansion. Tooth is VITAL. Management Tooth extraction or apicoextomy. Can’t just leave a tumour there. Hypercementosis vs. Cementoblastoma Marked difference in the appearance of the radiolucent rim. Hypercementosis is surrounded by a well-defined PDL space, and tends to be smaller and less round. NEOPLASTIC (Malignant) Osteosarcoma Definition Malignant mesenchymal neoplasm capable of DIRECTLY forming osteoid and/or bone. Most common presentation = growing, long bones, near knees in late teens. The disease that killed Terry Fox. 30% have lung metastases at time of diagnosis. Jaw lesions = 6%, average 1-2 decades older – young adults to 40s. See second increase incidence in people in their 60’s typically in the long bones and the flat bones in those with history of irradiation, or paget’s disease. Classification of Osteosarcoma Central (medullary) = most common Conventional osteosarcoma. Surface of bone. Parosteal osteosarcoma. Periosteal osteosarcoma. These variants tend to present in the long bones. Extra-Skeletal High grade osteosarcoma (rare). Clinical Presentation When you see cortical expansion and pain, put osteosarcoma on Diff Dx list. Tooth mobility, paresthesia, and nasal obstruction (maxilla) may be present. NOTE: symptoms may be present for prolonged periods, thus gnathic osteosarcomas potentially may be slow growing. Radiographic 3 most important subtypes Osteolytic (dissolving bone) = radiolucent Osteoblastic (radiopaque) Mixed Aggressive, destructive features. Classic “sunburst” pattern. “Spiking” root resorption. MRI and CT aid in evaluating extent of tumour. Hallmark of osteosarcoma imaging = infiltration from bone lesion, into adjacent soft tissue in “sunburst” pattern = 25% will have this pattern. Dense sclerotic change in the bone. Marked expansion in an irregular pattern – not following the contours of the bone. Widening of the PDL space. Superimposed mottled appearance. This patient presents with a 6cm painful expansion in the mandible. Treatment and Prognosis of intramedullary osteosarcoma Tx of extra-gnathic osteosarcomas Pre-op chemotherapy and radical surgical removal, with possible post-op chemotherapy. Prognosis = with this regimen, has improved to 80% survival at 5 years. Tx of gnathic osteosarcomas Wide surgical excision is treatment of choice (use of radiation/chemo is controversial) 5-year survival = 60-80% Metastasis to the lungs if anywhere. Death if occurs is usually due to uncontrolled local disease. Metastatic Bone Tumours More common than primary bone tumour. Carcinoma most common type. Adults = 80% are from lung, kidney, breast, prostate. More than 2/3 of breast, ¼ prostate, 1/3 lung and kidney cancer will have spread to the bone before the patient dies. Preferred sites: Spine Pelvis Ribs Skull Proximal long bones preferred sites. Clinical Presentation More than 80% of metastasis to the jaws occurs in the mandible. Most often patients experience pain, swelling, loosening of the teeth, a mass, or paresthesia. One particular presentation is called Numb-Chin Syndrome: Unexplained loss of sensation of the lower lip and chin. Occurs if the metastasis involves the mental branch of the inferior alveolar nerve. Common to see arise in a non-healing extraction site. On occasion, may be the initial presentation of a primary malignancy occurring in a different anatomic site. Radiology Appears as radiolucent defect – often having a moth-eaten appearance. May resemble periodontal disease when the PDL is involved. May see some radiopacities within the lesions or even a mixed lesion because of metaplastic new bone formation – seen in particular with breast and prostate cancer. Case Hard mass presenting intra-orally causing expansion of the lower face. Treatment of Metastatic Carcinoma Poor prognosis – osseous metastasis automatically puts the patient to stage IV cancer. Jaw involvement is almost always a sign of widespread disease = most patients (70%) are dead within 1 year. MORE DEVELOPMENTAL CONDITIONS Langerhans Cell Histiocytosis Definition A spectrum of a rare disorder characterized by proliferation of histiocyte-like cells in the presence of lymphocytes, plasma cells, multinucleated giant cells, and an increased number of eosinophils. 1-4 cases per million. Recall = Langerhans cells are usually found in the epidermis, mucosa, lymph nodes, and bone marrow – act as antigen presenting cells to T-lymphocytes. Debate whether neoplastic or reactive process. 40-60% are associated with BRAF mutation, with monoclonality noted in the Langerhans cells supporting the designation of a neoplastic process. Old classification Eosinophilic granuloma, monostotic, or polyostotic. Solitary or multiple bone lesions. Chronic disseminated histiocytosis. (Hand-Schuller-Christian Disease) with classic triad of bone lesions, exopthamos, diabetes insipidus. Bone, skin, and visceral involvement. Acute disseminated histiocytosis (Letterer-Siwe disease) Prominent skin, visceral, and bone marrow involvement. Mainly infants. Subclassifications (easier way) Single organ involvement Unifocal disease Multifocal disease Multi-organ involvement No organ dysfunction. Organ dysfunction Low risk (skin, bone, lymph node, pituitary gland) High risk (lung, spleen, bone marrow) Clinical Presentation Up to 20% of cases involve the jaws (usually posterior). Dull pain and tenderness. “Punched out”, but not corticated, radiolucencies. “Teeth floating in space” appearance. Histopathology Eosinophils distributed among histiocyte-like antigen presenting cells (kidney-shaped nuclei). These Langerhans cells stain positively for S-100 protein and CD1a. Management Curettage / intra-lesional corticosteroid injections. >3 bone involvement increases risk of progression/dissemination. More disseminated forms are managed with chemotherapy. Odontogenic Cysts Cyst Formation Basics Definition of a Cyst = Epithelium-lined cavity within the connective tissue. Any epithelium located within connective tissue can potentially form a cyst. Bone is a form of connective tissue, so any epithelium-derived odontogenic tissue can form cysts in the alveolar bone. Pathogenesis Something (ex: inflammation) stimulates 1 or more epithelial cells within CT to proliferate, forming a solid ball of epithelial cells. Beyond a critical radius, nutrients can no longer reach the center, resulting in apoptosis of epithelial cells. Fragmentation of these central cells creates an osmotic gradient, thus sucking in fluid. Fluid creates hydrostatic pressure increasing the size of the cyst. As long as the stimulus for epithelial proliferation persists, thickening of the epithelium continues. Centrifugal expansile growth of this “water-filled balloon” stimulates osteoclasts to resorb bone, and a bit further peripherally, osteoblasts to lay down bone creating a corticated margin. Between the pushing margin of epithelium and resorbing bone is a compressed fibrous “capsule” or “wall” of the cyst. Tissues of Odontogenic Origin = Any odontogenic cysts/tumours can arise from these tissues. DL = dental lamina EO = enamel organ (forms enamel) DP = dental papilla (forms pulp and dentin) DF = dental follicle Odontogenic Cysts General Principles Most are asymptomatic or may present with painless bony expansion. Unilocular. Any cyst that grows large enough can become multilocular. Corticated. Any cyst that becomes secondarily infected may lose its classic radiographic appearance. Any general “rules” you may learn about a given cyst will typically not apply if the cyst extends into the mandibular ramus. Although typically in bone, any odontogenic cyst can present in a peripheral presentation in the gingiva. Classification of Odontogenic Cysts Inflammatory Odontogenic Cysts Periapical (radicular) cysts Residual periapical cyst Buccal bifurcation cyst Developmental Odontogenic Cysts Dentigerous cyst Eruption cyst Lateral periodontal cyst Gingival cyst (adult and newborn) Glandular odontogenic cyst Odontogenic keratocyst (OKC) Calcifying odontogenic cyst INFLAMMATORY ODONTOGENIC CYSTS Periapical Cyst (Radicular Cyst) Definition Inflammatory cyst that develops from low-grade inflammation secondary to the non-vital pulp. Epithelium is derived from the cell rests of Malassez in the PDL. Clinical Presentation Presents at the apex of any tooth – epicenter of the cyst is around the tooth apex. Well-defined radiolucency. Corticated. Capable of large growth potential with expansion. Generally, not overly symptomatic unless secondarily infected. May cause root resorption. “Blunt” = no malignancy (periapical cyst). “Spiky” = may suggest malignancy (carcinoma). Lateral Radicular Cyst Radicular cyst associated with lateral canal. Histopathology Fibrous cyst wall lined by non-keratinized stratified squamous epithelium (SSNKE). Mixture of inflammatory cells. Centrally there is epithelial debris. Treatment When small, difficult to distinguish from a periapical granuloma – thus tooth is slated for RCT or extraction. If treated by RCT, may resolve. When large, or in associated with a previous RCT-treated tooth, more practical to treat with surgical root end surgery to enucleate the cyst or extraction of the tooth and the cyst. Always make sure to curette out the cyst if it doesn’t come out with the tooth. Residual Cyst Definition Periapical cyst that has not resolved after tooth extraction. Often will see a history of an extracted root canal treated tooth. Often stay fairly small as the inflammatory drive is no longer present. Inflammatory Collateral Cyst (Buccal Bifurcation Cyst) Definition Uncommon inflammatory odontogenic cyst associated with a vital tooth. Epidemiology Occurs in children, age 5-13 years. Occurs when the tooth is erupting. Clinical Presentation Buccal to the mandibular 1st or 2nd molars. Bony-hard swelling with tenderness. Foul-tasting discharge. Localized buccal periodontal pocket. Molar crown tipped buccally, apices lingually. Proliferative periostitis, from secondary infection common. 33% bilateral. Management Histopathology is equivalent to radicular cyst. Treated with enucleation – extraction of tooth NOT necessary. Complete healing 1 year post-op, normal pocket depth, radiographic bone fill. Tooth may not return to its proper position within the arch. DEVELOPMENTAL ODONTOGENIC CYSTS Dentigerous Cyst Definition A developmental cyst that is lined by reduced enamel epithelium and is attached to the CEJ of the tooth. Most commonly presents in association with impacted third molars and canines. Epidemiology More commonly presents in teenagers and young adults. Clinical Radiographic Features Periphery and Shape Well-defined, corticated, with a curved outline. Inserts at or near the CEJ of the tooth. Internal Structure Radiolucent except for the crown of the tooth it surrounds. Effect on surrounding structures. Displacement and/or resorption of adjacent teeth. Apical displacement of the affected tooth. May displace the IAN canal inferiorly. May expand the cortex of the jaws or elevate the sinus floor. Histology Thin, non-keratinized stratified squamous epithelium (SSNKE) = same as radicular cyst. If inflammation is present, may see elongated and interconnected rete ridges. Inactive odontogenic cell rests are often seen within the CT wall. Clinical Info: Here is a cystic structure associated with tooth 36, what is it? All cysts look similar histologically (radicular cyst, inflammatory collateral cyst, or dentigerous cyst). Must use clinical presentation to make a diagnosis. Treatment Enucleation of the cyst and usually extraction of the tooth. NOTE: can attempt to keep the tooth after the enucleation if desired. Ex: an impacted canine is exposed and fitted with an orthodontic bracket to be repositioned into the arch. NOTE: not all radiolucencies around the crown of an erupting tooth represent a dentigerous cyst. If the radiolucency is small, may be dealing with a hyperplastic dental follicle. <5mm = hyperplastic dental follicle. >5mm = dentigerous cyst. Eruption Cyst (AKA eruption hematoma) Definition Soft tissue equivalent to a dentigerous cyst. May be pink or blue. Typically, no Tx is required as the tooth will eventually erupt. Could consider “unroofing” the soft tissue overlying the tooth. Lateral Periodontal Cyst Definition Uncommon developmental cysts that arises from epithelial rests of dental lamina (cell rests of Serres) Epidemiology 5th-7th decades, rarely in people <30yrs. 75-80% mandibular premolar/canine/lateral area. Clinical and radiographic features Well-circumscribed radiolucent area lateral to the roots of vital teeth. May be tear drop shaped. Usually, <1cm. Lamina Dura is often resorbed around affected teeth. May cause splaying of the teeth. Rare variant = multilocular and capable of more significant growth: botryoid odontogenic cysts. Histology Thin fibrous wall lined by SSNKE. Most areas 1-3 cell layers thick. Focal nodular thickenings (plaques/theques). Treatment Conservative enucleation. Recurrence unusual although the botryoid variant more likely to recur. Gingival Cyst of the Adult Soft tissue counterpart of the lateral periodontal cyst. Derived from rests of dental lamina (Serres). Most in mandibular canine-premolar area on the buccal. Asymptomatic, usually <5mm. Blue gray. Underlying bone may be “cupped out”. Shares the same histology as lateral periodontal cyst. Treatment Conservative excision (excellent prognosis). Odontogenic Keratocyst (OKC) Definition Developmental cyst arising from the cell rests of dental lamina. Thought to have some type of intrinsic growth potential. In the past, has been called a tumour because of this tendency. Does not behave like a cyst. It burrows through the bone without much expansion. Epidemiology Wide age range = 60% in age 20-40 yrs (younger adults). Clinical Presentation Can arise anywhere in the jaws and with any relationship to the tooth! 60-80% of cases in mandible, mostly in posterior mandible. Asymptomatic and grows with little bony expansion. Unlike other cysts. If bone is expanded, probably not an OKC. Can be multifocal. Nevoid basal cell carcinoma syndrome (Gorlin-Goltz Syndrome). Radiographic features Well-defined radiolucency sausage shape. Typically, corticated margin. 25-40% of cases are associated with an unerupted tooth (when the radiolucency first appears to insert below CEJ = probably OKC.) Multilocular only if large. Seldom expands cortex. May push teeth or less commonly resorb roots. Seldom peforates cortex. Histopathology Thin fibrous wall lined with epithelium that displays: Uniform layer of SSKE (6-8 cells thick). Epithelium/CT interface is flat. Parakeratinized. Corrugated surface. Palsaded basal cells (columnar/cuboidal). Within the fibrous wall, often will see small daughter cysts that have separated form the original cyst, which results in higher recurrence rate. Treatment Enucleation/curettage with ostectomy of peripheral bone (in the past treatment with Carnoy’s solution, 5’FU or liquid nitrogen). Frequency of recurrence aprox 30-60% with simple enucleation. Recurrence can occur late (usual 5 years, but can be up to 10 years). Larger lesions – consider marsupialization prior to definitive treatment to reduce cyst size and regenerate bone. Marsupialization = the surgical technique of cutting a slit into a cyst and suturing the edges of the slit to form a continuous surface from the exterior surface to the interior of the cyst. Sutured in this fashion, the cyst remains open ad can drain freely. Consider investigation for Gorlin syndrome (basal cell carcinoma nevoid syndrome) if multifocal presentation. Nevoid Basal Cell Carcinoma Syndrome Autosomal dominant inherited condition with a mutation of the PTCH (patched) gene. Characterize by: Multiple basal cell carcinomas of the skin. OKCs. Bifid ribs. Epidermal cysts. Calcified falx cerebri. Rib abnormalities. Palmar/plantar pits. Prevalence = 1 in 60,000. Additional findings (<50%) Ovarian fibromas. Strabismus. High incidence of medulloblastomas. Brachymetacarpalism. Menigngioma. Cardiac fibroma. Fetal rhabdomyoma. Cleft lip and palate. Treatment/Prognosis. Management of BCC’s, KCOT/OKCs, and additional tumours. Genetic counselling. Reading = Rarer cysts Orthokeratinized odontogenic cyst Definition Developmental cyst that comparable to an odontogenic keratocyst (OKC) but has orthokeratinized epithelium instead of parakeratinized epithelium. Epidemiology Mostly young adults. 2:1 male to female. Most often involving an unerupted mandibular third molar, presenting as a unilocular pericoronal lesion. Histopathology Orthokeratinized stratified squamous epithelium. Prominent keratohyaline granules. NO palisaded basal cell layer like in odontogenic keratocyst (OKC). Treatment Enucleation and curettage. Rarely recurs (no daughter cells and 2% recurrence). Not associated with Gorlin Syndrome. Glandular Odontogenic Cyst Definition Rare developmental odontogenic cyst that has a very strong predilection for the anterior regions of the jaws. Contains glandular elements: ducts, goblet cells within the epithelial lining. Epidemiology Middle-aged adults (average 48yrs old). Clinical/radiographic Presentation Anterior region of the jaw. Many cross the midline. Typically, unilocular radiolucency with well-defined margins with sclerotic rim. Can become multilocular when larger. Expansion and thinning of the cortex. Histology Plaques/theques (nodular thickenings) Similar to lateral periodontal cyst/gingival cyst of the adult. Glandular features within the epithelium Ex: small ducts, goblet cells Treatment Treated initially with enucleation. Rate of recurrence 20-30% (higher if multifocal). If recurs, treated more aggressively with en bloc resection. Calcifying Odontogenic Cyst = COC Definition Uncommon. May be associated with other odontogenic tumours (odontomas, AOT, ameloblastoma) 65% of cases in incisor/canine area = anterior region. Most cases diagnosed in 2nd/3rd decades (teenagers and young adults). Neoplastic variant occurs in older patients. Clinical Presentation Unilocular radiolucency. May be multilocular when large. Well-demarcated borders. Often: thin sclerotic rimming. Eventually: irregular radiopacities. Around crown of tooth: 1/3-1/2 of cases. Usually 2-4cm, may be much larger. Cortical thinning and expansion. Histopathology Odontogenic epithelial lining of 4-10 cells thick, basal cells may be cuboidal/columnar and are similar to ameloblasts (reverse polarization). Ghost cells = altered epithelial cells that have lost their nuclei but retained their cell outline (often will have varying degrees of calcifications over time = radiopaque). “Keratinocytes that have lost their nuclei”. Treatment Simple enucleation – only a few recurrences have been reported. If associated with another odontogenic tumour: treatment and px same as for the associated tumour. Nasopalatine Duct Cyst Definition A developmental cyst arising from vestigial epithelium within the nasopalatine duct. Arises between floor of nose and incisive papilla. NOT OF ODONTOGENIC ORIGIN. Epidemiology 4-6th decade. 3X more common in men. Clinical Presentation Often inflamed and tender. Slow, limited growth. May cause numbness or burning on anterior palate. Can be partially in soft tissue and paritally in bone. When entirely in soft tissue – renamed to “cyst of the incisive papilla”. Can fluctuate in size: come and go with draining salty tasting fluid. Radiographic Well-defined radiolucency. Corticated. 0.6-6cm. May cause cortical expansion and divergence of the roots of the teeth. Histopathology SSNKE, or pseudostratified epithelium, columnar, or cuboidal. Capsule usually inflamed, probably due to communication with nasal or oral cavity. Neurovascular components of incisive canal seen within the wall (required for definitive Dx). Small island of normal cartilage (“cartilaginous rest”) occasionally found. Treatment Simple curettage. Rarely recurs. Epidermoid/Desmoid Cyst of the Oral Cavity Definition Uncommon developmental cystic malformation that is lined by epidermis-like epithelium and contains dermal adnexal structures (hair follicles) in the cyst wall. It is considered the benign cystic form of a teratoma. Clinical Presentation Midline of the FOM, although they can be displaced laterally. May develop above or below the geniohyoid muscle and thus will produce a swelling under the tongue, or a swelling in the submental area (looks like a double chin). Can be quite large – from a few mm to 12cm. Can cause problems with speech or breathing if they lift the tongue. Doughy and rubbery that will retain pitting when compressed. Histology of Epidermoid/Desmoid Cyst SS ortho-hyperkeratinized epithelium linign a cystic space with a prominent granular cell layer. Dermoid cyst = Adnexal structures in the cyst wall (ex: hair follicle, sebaceous glands) Epidermoid cyst = no adnexal structures. Treatment Surgical removal. Recurrence uncommon. Rare malignant transformation to SCC has been reported. Odontogenic Tumours Classification of Odontogenic Tumours Based on Cell of Origin Tumours of Odontogenic Epithelium (Dental lamina + enamel organ) Mixed Tumours (Odontogenic epithelium + ectomesenchymal tissue with or without dental hard tissues) Includes cells of both enamel organ and dental papilla Tumours of Ectomesenchymal Tissue (cells of the dental papilla) Odontogenic Tumours General Rules Odontogenic Rumours in general are very uncommon. Odontogenic tumours are generally BENIGN, although some may exhibit aggressive behaviours. Some malignant odontogenic tumours do occur but are extremely rare (we will not be discussing in this class). General Clinical Presentation Presentation ranges as an incidental finding to an asymptomatic expansile mass. Not unlike the behaviour observed for odontogenic cysts. Although any tumour when it is small enough could be unilocular, certain odontogenic tumours have a strong propensity to present as multilocular lesions. Odontogenic tumours may or may not be associated with a tooth. Odontogenic Epithelium Tumours (benign) Ameloblastoma Conventional, Unicystic, Extra-osseous/peripheral, or Metastasizing Adenomatoid Odontogenic Tumour (AOT) Calcifying epithelial odontogenic tumour (rare) Squamous odontogenic tumour (rare) Ameloblastoma (conventional) Definition Benign tumour of odontogenic epithelium. Huge growth potential. Infiltrative growth pattern and thus high recurrence rate if simply curetted. 90% recurrence after simple curettage. Can extend into base of the brain and cause death if posterior maxillary lesion is not completely excised. Clinicopathologic Types Conventional Unicystic Peripheral Metastasizing (very rare) Epidemiology RARE under the age of 10. Uncommon in 10-19 years old. Equal prevalence in 3rd to 7th decade. 80-85% occur in the mandible (usually posterior). Clinical Presentation Painless swelling or expansion. Capable to significant growth if left untreated. Pain and paresthesia are uncommon. Radiographic Multilocular radiolucency (soap bubble or honeycomb appearance). Expansile lesion with thinning of the cortices. Found in any relation to the teeth or with no adjacent tooth. Radiographic margins range from well- to ill-defined, but usually are somewhat defined. Root resorption is common. Histopathology Diagnostic features Hyperchromatic nuclei of ameloblast-like basal epithelium. Stellate reticulum-like cells. Some discrete keratin formation in the middle. An ameloblastoma island is like an inverted dental organ, with the ameloblastoma-like cells on the periphery (note the reverse polarization). Unicystic Ameloblastoma Definition Cystic tumour lined by odontogenic epithelium that has a low recurrence rate. Epidemiology Tend to present in second decade most commonly. 90% in mandible – predilection for the posterior. Clinical and Radiographic Presentation Unilocular, pericoronal radiolucency. Would be rare to see a unicystic ameloblastoma not around a tooth. Variants of Unicystic Ameloblastoma Intraluminal Papillary appearance to the lumen of the tumour (gross appearance). Plexiform growth pattern in the odontogenic epithelium. Luminal Mural Treatment for Ameloblastomas Unicystic = enucleation. Conventional = En bloc resection. Management and Prognosis of Ameloblastomas Conventional (conventional and mural) 5-17% recurrence rate with resection. 30-35% with curettage or enucleation. Unicystic (luminal and intraluminal) 6-37% recurrence. Peripheral ameloblastoma No recurrence with simple excision. Adenomatoid Odontogenic Tumour = AOT Definition Uncommon benign tumour of odontogenic epithelium. Epidemiology Teenagers – rarely over age 30. Strong female predilection (2:1) Loves the maxilla (2:1). Clinical Presentation Rule of 2/3 2/3 adolescents. 2/3 females. 2/3 maxilla. 2/3 associated with unerupted root. Radiographic Initially radiolucent flocculent opacities (“snowflakes”) Pericoronal presentation tends to be apical to CEJ. Tends to displace teeth versus resorbing them. Histopathology Round organoid masses of spindle-shaped epithelial cells (rosette-like structures) and duct-like epithelial structures. Mature lesions can contain calcifications – attempts at forming dentin, cementum, or enamel. Treatment Encapsulated – thus enucleates cleanly on curettage. When a tooth is involved, the tooth is extracted. Rarely recurs. Calcifying Epithelial Odontogenic Tumour (CEOT) = “Pindorg Tumour” Definition Benign, aggressive neoplasm of stellate intermedium and/or reticulum. Less aggressive than ameloblastoma though. Epidemiology and Clinical Presentation Rare (<1% of odontogenic tumours) Age = 30-50 years. Location = Md > Mx, Posterior > Anterior Most common presenting sign is a painless, slow-growing swelling. Radiographic Presentation Unilocular (more in maxilla) or multi-locular. Margins are typically scalloped and well-defined; may be corticated or ill-defined. Frequently associated with an impacted tooth (most often a mandibular molar). Contains calcified structures of carrying size and density. Expansile. Histopathology Clusters of polyhedral epithelial cells. Often: intercellular bridges. Large and dysplastic-looking cells. Background fibrous stroma. Amyloid-like extracellular material; positive for congo red, which exhibits an apple-green birefringence when viewed under polarized light. Calcifications with concentric rings form in the amyloid-like areas (Liesegang rings). Treatment Conservative local resection with a narrow rim of bone is the Tx of choice. Recurrence rate is 15% (highest with curettage as Tx). Prognosis is typically good, but rare lesions can exhibit aggressive or malignant behaviour. Mixed Epithelial/Ectomesenchymal Tumours Ameloblastic Fibroma Compound and Complex Odontomas Ameloblastic Fibroma Clinical Presentation Younger individuals (<20 years) Frequently occurs in the posterior mandible. Unilocular or multilocular radiolucency. Associated with an unerupted tooth (75% of time). Histopathology Epithelial and mesenchymal components. Epithelial component = cords and small islands of odontogenic epithelium. Mesenchymal component = dental papilla. Treatment Conservative initial therapy, although ongoing debate as to best treatment because of danger of recurrence. More aggressive surgical excision for recurrent lesions. VERY rare incidences of malignant transformation (ameloblastic fibrosarcoma). Odontomas Definition Developmental anomalies (hamartomas) versus true tumours. Unlike neoplasms, under fairly normal growth regulation (i.e., stop growing when normal counterparts = teeth do). 2 types Compound = small toothlike structures. Predilection for anterior maxilla. Complex = no anatomical resemblance to a tooth. Predilection for molar regions. Clinical Presentation Typically, asymptomatic although often prevent a permanent tooth from erupting. Usually not much larger than the size of a normal tooth. Occasionally can be larger (up to 6cm) and cause jaw expansion. Can rarely present peripherally. Radiographic Approximates opacity of teeth. Has PDL equivalent = radiolucent rim. May have lamina dura equivalent (thin cortication). Compound Odontoma Multiple irregularly shaped miniature teeth removed from within the capsule of a large compound odontoma. Histology Compound odontoma has mini teeth. Complex odontoma has normal denture tissues at the microscopic level = pulp, dentin, cementum, enamel, dental follicle. Treatment Easily curetted out, including entire dental follicle equivalent, excellent prognosis. Ameloblastic Fibro-Odontoma Tumour with general features of an ameloblastic fibroma, but also contains enamel and dentin. Some likely represent immature odontomas, while other likely represent true tumours capable of significant growth. Epidemiology Children (average age = 10yrs old) Predilection for posterior jaws (mandible). Often associated with an unerupted tooth. Clinical Presentation Usually unilocular, radiolucent with internal radiopacities equivalent to enamel and dentin. May cause expansion if large. Histology An ameloblastic fibroma (cords of odontogenic epithelium + dental papilla like connective) component. Calcified component = foci of enamel and dentin matrix. Treatment Curettage, with excellent prognosis and usually does not recur. Ectomesenchymal Tissue Only Odontogenic Myxoma Cementoblastoma Odontogenic Myxoma Epidemiology Any age but usually in young adults (25-35) Any area of the jaw, but usually mandible. Clinical and radiographic presentation Painless jaw expansion. May hav