BOARD REVIEW ORAL PATHOLOGY Developing a differential diagnosis -Types of lesions: Macule Plaque Papule Nodule Erosion Ulceration

Vesicle Bullae -Macule: entirely flat; usually pigmented. -Plaque: slightly elevated with flat surface. -hyperkeratosis: thickening of the keratin layer of the surface epith. -orthokeratin: has a granular cell layer, but nuclei are lost. -parakeratin: more rapid onset; nuclei are present, but no granular cell layer. -acanthosis: thickening of the spinous cell layer (middle layer). -spongiosis: acanthosis with intercellular edema. -Papule: a circumscribed elevated area <5mm in diameter; usually white or pink. -Nodule: an elevated area of mucosa >5mm in size; often pink. -Erosion: partial loss of epith; basal layer in tact (so, not completely through epith.) -Ulceration: full thickness loss of epith covering of oral mucosa. Floor may appear yellow, gray-white, or red. -Vesicle: a raised fluid filled lesion <5mm in diam; generally contains clear fluid. If filled with pus, its called a pustule. -Bullae: a large fluid filled lesion >5mm in diameter. -Sessile: a growth pattern where the base is the widest part of the lesion. -Pedunculated: a growth pattern where the base is narrower than the widest part of the lesion. -Papillary: numerous rounded surface projections (cauliflower-like) arising from a thin stalk. -Verrucous: a rough or warty surface (church-spire-like) with hyperorthokeratinization. Principles of Biopsy -Excisional biopsy: performed if 1cm or less. -Incisional biopsy: performed if greater than 1cm. Three types of incisional biopsy: -wedge: best for deep lesions -punch: best on flat surfaces -shave: if cosmetics are not a concern---this type is discouraged -Cytologic smear: only indicated for fungal, not for dysplasia -Needle biopsy: 2-types: -needle core (not done in oral cavity) -fine needle aspiration: 25ga or less, one anterior hole -Toluidine blue: -not a screening tool to tell what a differential might be -not good in areas of hyperkeratosis -stains where nuclei are, so is shows where to biopsy and the extent of the lesion -should never be used to determine if a biopsy is necessary -Grading & Staging: TNM
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-Grading T = Tumor -T0 = no evidence of primary tumor -Tis = carcinoma-in-situ -T1 = tumor <2cm -T2 = tumor >2cm & <4cm -T3 = tumor >4cm -T4 = tumor invasive of deep structures N = Node -N0 = no nodal involvement -N1 = single ipsilateral node <3cm -N2a = single ipsilateral node >3cm, but <6cm -N2b = multiple ipsilateral nodes, but none >6cm -N2c = bilateral or contralateral lymph nodes, but not >6cm -N3 = nodes, at least one >6cm M = Metastases -M0 = no known metastases -M1 = distant metastasis present Staging -Stage 0 = Tis N0 M0 -Stage 1 = T1 N0 M0 -Stage 2 = T2 N0 M0 -Stage 3 = T3 N0 M0; & T1, T2, or T3 with N1 M0 -Stage 4 = T4 with any N1 M0 any T with N2 M0, or N3 M0 any T, any N with M1 -Fixation & Transport: -Formalin = 37% formaldehyde & 63% water -this is the most formaldehyde that can be put into water without separating out. -10% formalin is 3.7% formaldehyde -Michels solution: used for anything you need immunofluorescence. Oral Manifestations of Systemic Diseases I. Infectious etiology A. Syphilis -causative organism: Treponema pallidum (direct contact/not airborne) 1. Primary stage: -chancre (appears in about 3 weeks) -see spontaneous healing 2. Secondary stage: -see 4-10 wks after infec. -see maculopapular rashes -mucous patches -condyloma lata (papillary lesions that resemble viral papillomas) -lues maligna: seen in immunocompromised patients
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-spontaneous healing in 3-12 weeks 3. Tertiary stage: -develops after a latent period & patient not infected at this point -gumma: large tissue destruction, ulceration -leutic glossitis: atrophy and loss of dorsal tongue papillae -CNS manifestations (3): psychosis, dementia, & death 4. Congenital syphilis: -characterized by Hutchinsons Triad: -Hutchinsons teeth: incisors & molars (screwdriver incisors/mulberry molars) -Interstitial keratitis -8th nerve deafness -other congenital aspects (4): saddle nose deformity, high arched palate, frontal bossing & a short maxilla II. Immune mediated A. Sjogrens syndrome -2 major hallmarks: keratoconjunctivitis sicca (dry eyes) & xerostomia (dry mouth) 1. Primary form: occurs alone (40%) w/ dry eyes and dry mouth 2. Secondary form: occurs with another autoimmune disorder like RA (most common one), SLE, or scleroderma -see bilateral swelling of parotid glands -may see red/tender oral mucosa due to candidiasis B. Wegeners granulomatosis -The triad 1. Focal necrotizing vasculitis of upper airway and lung. 2. Necrotizing granulomas of upper & lower resp tract. 3. Necrotizing glomerular nephritis. -Oral manifestations (3): strawberry gingivitis, nonspecific ulceration, & enlargement of the salivary glands. III. Neoplastic/Malignant A. Langerhans cell histiocytosis (histiocytosis X) 1. Acute disseminated Letterer-Siwe Disease: -mainly in infants -maculopapular rash, lymphadenopathy -50% 5-year survival if under age 2; 90% survival if over age 2. 2. Unifocal Eosinophilic Granuloma: -mainly in adults -solitary bone lesions/teeth floating in air -tx with curettage/tx less accessible lesions with radiation 3. Multifocal Hand-Schuller-Christian Disease -mainly in adolescents -see punched out bone lesions -see tooth loss/generalized periodontitis
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-50% spontaneously resolve; 50% need chemo -Hand-Schuller-Christian Triad: a. bone lesions (punched out)(skull, ribs, vertebrae) b. exophthalmos c. diabetes insipidus -EM shows Birbeck granules B. Hyperparathyroidism 1. Primary HPT: overproduction of PTH from an adenoma (80-90%). 2. Secondary HPT: due to renal failure (constant PTH production due to low serum calcium). 3. Clinical features: ** stones, bones, moans, & groans a. Stones: urinary tract stones due to high calcium b. Bones: subperiosteal resorption of index/middle finger c. Moans: personality changes, depression, confusion d. Groans: abdominal pain, peptic ulcers 4. Radiographic findings: central giant cell lesions, loss of lamina dura 5. Histo: brown tumor of HPT (looks like central giant cell granuloma) 6. Txmnt: -Primary: remove tumor -Secondary: Vit D.; renal transplant C. Leukemia -malignant neoplasms of hematopoietic tissue -could be myeloid or lymphocytic (depends on origin) -often a genetic event: Philadelphia chromosome: translocation of the long arm of chromosome 22 to 9. -clinical findings: fatigue, fever, palatal petechiae, ecchymoses, gingivitis (hemorrhagic gingivitis/spontaneous bleeding). D. Lymphoma 1. Non-Hodgkins Lymphoma -initially arises in lymph nodes and seen as solid masses (usually painless lymphadenopathy) -radiographic findings: ill-defined, ragged RL 2. Hodgkins Lymphoma -separate from non-Hodgkins due to the presence of the Reed-Sternberg cell. -rare oral involvement IV. Other A. Gingival hyperplasia -Usually due to 3 medications: 1. Dilantin (phenytoin) 2. Calcium channel blockers (Procardia, Verapamil, Calan) 3. Cyclosporine B. Amyloidosis -Amyloid: a proteinaceous material consisting of glycoproteins (systemic) -5 types of amyloidosis: 1. Primary: no known predisposing factors
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C.

D.

E.

F.

G.

2. Secondary: result of TB, osteomyelitis, sarcoid. 3. Myeloma associated 4. Hemodialysis associated 5. Familial -Clinical features: 1. nodules on tongue 2. waxy papules on skin (eyelids) 3. enlarged tongue is not unusual Crohns disease -A chronic inflammatory process of the alimentary tract---primarily in the colon, resulting from fistula formation. -Clinical features: oral lesions appear as diffuse nodular swellings (cobblestone appearance), aphthous ulcers. Can wax and wane. Pernicious anemia -Cause: lack of intrinsic factor---leads to negation of absorption of extrinsic factor. -It ultimately affects DNA synthesis, RBC maturation, megaloblastic anemia. -Clinical features: painful, burning tongue; glossitis, beefy red tongue; yellow tinged mucosa. Iron deficiency anemia -gastric mucosal degeneration from low iron---caused malabsorption. -see microcytic anemia -Chronic iron deficiency anemia = Plummer-Vinson Syndrome -microcytic (small) hypochromic (decreased Hb) anemia. -clinical features: esophageal webs, koilonychia (spoonshaped nails). -oral signs: smooth red burning tongue, filiform papillae absent, decreased fungiform papillae, angular cheilitis. Sickle Cell Anemia -A genetic disorder resulting from a substitution of thymine for an adenine in DNA. -The trait is heterozygous, the disease is homozygous. -Clinical aspects: -the sickled RBCs are more fragile and block capillaries b/c of their shape. -crisis produced by infection, hypothermia, & hypoxia---produces ischemia, infarction, or tissue death. -Oral manifestations: -gingival hemorrhage -reduced mandibular trabecular pattern -** hair-on-end appearance on skull films (like in thalassemia) Sarcoidosis -A multi-system granulomatous disorder of unknown cause. -Clinical features: -bi-lateral hilar lymphadenopathy -cough, dyspnea, fever, weight loss, fatigue -mostly seen in lymph nodes, lungs, salivary glands -Diagnose by elevated serum ACE levels.
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H. Pagets Disease (osteitis deformans) -A chronic slow-growing progressive disease of unknown cause characterized by alternating resorption and deposition of bone resulting in weakened and distorted bones. -4 possible causes: genetic, inflammatory, endocrine, or viral (most likely) -Clinical features: -mostly males -more often polyostotic rather than monostotic -bone pain -progressive skull circumference -maxilla more common than mandible -Radiographic features: -early stage: decreased radiodensity of bone -osteoblastic stage: class cotton wool appearance. -teeth: pronounced hypercementosis -Lab results: elevated serum alkaline phosphatase, but normal calcium & phosphorus levels. -Complications: denture fit problems, deafness, visual, & osteosarcoma (113%). Soft tissue cysts I. Dental Lamina Cysts of the Newborn A. Gingival cysts of the newborn: -origin: post-functional rests of dental lamina. -clinical presentation: white soft tissue nodules on alveolar ridge of infants. -txmnt: none B. Epsteins Pearls: -origin: epith entrapped in midline of hard palate. -clinical presentation: multiple small white nodules along midline of hard palate. -txmnt: none C. Bohns Nodules: -origin: epith entrapped from minor salivary glands -clinical presentation: multiple small white nodules found distributed primarily on the soft palate and posterior hard palate. -txmnt: none II. Cysts of the Adult A. Gingival cyst of the adult: -origin: post-functional rests of dental lamina. -may be the extra-osseous counterpart of the lateral periodontal cyst. -clinical presentation: solitary well-circumscribed, small, non-tender soft tissue nodule on free or attached gingiva. -most common location: mandibular gingiva in premolar, canine, or lateral incisor area. -seen in middle aged adults/no radiographic findings. -txmnt: surgical excision.
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B. Nasolabial cyst: -origin: nasolacrimal duct. -clinical presentation: swelling of the mucolabial fold and floor of nose. -no radiographic features. -txmnt: surgical enucleation/no tendency to recur. C. Lymphoepithelial cyst: -origin: cystic transformation of epithelium present within the oral lymphoid tissue. -clinical presentation: well-circumscribed yellow soft tissue nodule. -most common location: floor of mouth and ventral surface of tongue. -txmnt: surgical enucleation/no tendency to recur. D. Branchial cleft cyst: -origin: cystic transformation of salivary gland tissue present in cervical lymph nodes. -clinical presentation: well-circumscribed, freely movable mass along the anterior border of the SCM. -txmnt: surgical enucleation/no tendency to recur. E. Thyroglossal duct cyst: -origin: remnants of the thyroglossal tract running from the foramen cecum to the thyroid gland. -clinical presentation: midline of neck or to one side---may also be found on floor of mouth, tongue, or near the thyroid cartilage. F. Epidermoid and Dermoid cysts (Sebaceous cysts): -origin: epithelium trapped in C.T. during embryogenesis. -clinical presentations: well circumscribed, compressible, soft tissue enlargement found in the floor of the mouth, submandibular areas & sublingual areas. -dermoid cyst has sebaceous glands, hair follicles, & sweat glands in the cyst wall. The epidermoid cyst does not. -txmnt: enucleation/little to no recurrence. G. The Spurious cysts: 1. Nasopalatine duct cyst: -the most common non-odontogenic cyst of the jaws. -common time period of occurrence: 4th, 5th, & 6th decades of life. -radiographic appearance is heart shaped and may cause teeth to test nonvital, but vital after cyst is removed. -txmnt: enucleation/recurrence is rare. 2. Median palatal cyst: -very rare and must be separated from the nasopalatine foramen. -a true fissural cyst. -to be considered a true median palatal cyst, it must be separate from the nasopalatine duct. 3. Median alveolar cyst: -does not exist. 4. Nasolabial cyst: see above Pathology of the Teeth
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I. Alterations in numbers of teeth A. Decreases in the numbers of teeth 1. anadontia: all teeth missing 2. hypodontia: less teeth than expected 3. oligodontia: at least 6 teeth are missing 4. true anadontia: the teeth never formed; developmentally missing 5. false anadontia: the teeth formed, but subsequently extracted 6. pseudoanadontia: teeth appear missing, but are impacted (3rd molars, max laterals, mand 2nd premolars. B. Increases in the numbers of teeth 1. hyperdontia: too many teeth 2. supernumerary tooth: tooth at least approached normal size a. mesiodens: most common b. distomolars: 4th molars 3. accessory tooth: looks like a tooth, but is much smaller than would normally be expected a. paramolars: facially or lingually in the max post areas II. Alterations in size of teeth A. Decreases in the size of teeth 1. generalized microdontia: all teeth affected a. true generalized microdontia: teeth reduced in size (pituitary dwarfism) b. relative generalized microdontia: large jaw size makes teeth look smaller 2. localized microdontia: isolated teeth affected a. 3rd molars and peg laterals B. Increases in the size of teeth 1. generalize macrodontia: all teeth affected a. true generalized macrodontia: teeth are increased in size (pituitary gigantism) b. relative generalized macrodontia: small jaw size makes teeth look larger 2. localized macrodontia: isolated teeth affected a. often associated with hemifacial hypertrophy

III.

Alterations in shape of teeth A. Crown involvement 1. Shovel shaping: thickened mesial and distal marginal ridges on incisor teeth. May be associated with dens invgaginitis or dens evaginitis. 2. Accessory cusps: a. Cusp of Carabelli: most common; palatal surface of ML cusp of max molar tooth. b. Talon cusp: lingual surface of max incisor or canine teeth
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c. Doaks cusp: accessory cusp found on buccal surface of molars d. Dens evaginitis: accessory cusp emanating from the central groove of premolar teeth. 3. Gemination: -one tooth bud attempts to make two teeth -2 crowns, one single root -maxillary perm incisors most common (count the teeth) 4. Fusion: -two teeth joined with fusion of their dentin -often one crown with 2 complete roots -probably due to 2 tooth buds developing close together B. Root involvement 1. accessory roots (supernumerary roots---usually molars) 2. dilaceration: unusual curvature of the root; likely cause is trauma 3. enamel pearl: most commonly found in the furcation area of molars 4. tauradontism: bull teeth a. hypertauradont b. mesotauradont c. hypotauradont 5. concrescence: fusion of teeth via cementum 6. hypercementosis: excessive production of cementum on the root surface a. etiologic factors (PIG ON TAP): Pagets disease, idiopathic, giantism, occlusal trauma, non-functional tooth, trauma, acromegaly, periapical granuloma. IV. Alterations in structure of teeth A. Amelogenesis imperfecta: -only enamel is affected -see early & easy loss of enamel. -no increased incidence in caries since secondary dentin forms readily B. Dens invaginitis (dens in dente): a tooth developing within a tooth 1. coronal: most common (laterals mostly) 2. radicular: rare C. Dentinogenesis imperfecta: -developmental disturbance in dentin formation in the absence of systemic disease. Dentinal tubules are less numerous and larger -2 types: 1. isolated (involving only one tooth) 2. in conjunction with osteogenesis imperfecta -defective DEJ allow easy fracturing off of enamel -the dentin abrades rapidly -clinical appearance of teeth: brown opalescent (translucent hue), bulbous crowns with marked cervical (CEJ) constriction, & obliteration of pulp chambers and root canals on radiographs. D. Dentinal dysplasia: 1. 2 classifications: a. Type I: Radicular dentin dysplasia
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-rootless teeth -crowns appear normal, roots missing in rudimentary form b. Type II: Coronal dentin dysplasia -deciduous teeth exhibit similar opalescent hue -radiographs show bulbous crowns -root length is normal in both dentitions -permanent teeth show thistle-tube shaped pulps E. Regional odontodysplasia (ghost teeth) -teeth appear deformed clinically -markedly enlarged pulp chamber -radiographic appearance is the ghost of a tooth F. Vitamin D resistant rickets (Hypophosphatemia) G. Hypophosphatasia: enzyme production deficiency V. Alterations in color A. Fluorosis -seen when fluoride content of drinking water exceeds 1ppm -as fluoride level increases, hypoplasia of enamel and brown discoloration occur (see chalky surface to enamel) B. Tetracycline staining -tetra gets incorporated into hard tissues during development -colors: yellow, gray-brown, green to gray to black Bone Pathology of the Head and Neck I. Inflammatory & reactive lesions A. Acute osteomyelitis -clinical: swelling over affected area, may see sequestrum formation, predisposition to chronic systemic disease -radiographic appearance: unremarkable to an ill-defined radiolucency -txmnt: -drainage -antibiotics for at least 6 weeks after drainage has stopped B. Chronic osteomyelitis -clinical: a direct extension from acute osteomyelitis with swelling, pain, sinus formation, purulent discharge, sequestrum formation, tooth loss, & pathologic fracture. -radiographic appearance: patchy, ragged, irregular radiolucency---onion skinning. -txmnt: surgical removal of all infected material down to sound bleeding bone, IV antibiotics in high doses, and hyperbaric oxygen therapy if resistant to normal txmnt. C. Osteoradionecrosis (ORN): bones rxn to radiation---bvs destroyed; O2 cannot permeate through vessels---does not require an infection to occur. -clinical: significant incidence with greater than 7500 rads. -radiographic appearance: ill defined areas of RL that may develop zones of RO as the dead bone separates from the residual non-vital bone.

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-txmnt: PREVENTION is the key; but removal of sequestra, irrigation, antibiotics, hyperbaric oxygen, and possible radical resection of involved bone. Try to complete dental work 3wks prior to radiation. D. Pagets Disease: -clinical: cc of bone pain and progressive enlargement; high serum alkaline phosphatase, but normal calcium and phosphorus. -radiographic appearance: cotton wool, teeth with hypercementosis E. Langerhans cell histiocytosis: -clinical: dull pain and tenderness, periodontitis -radiographic appearance: punched out radiolucencies, teeth floating in air -txmnt: bone lesions treated with curettage. F. Simple bone cyst (Traumatic bone cyst, Idiopathic bone cavity): -clinical: usually asymptomatic -radiographic appearance: well-delineated RL defect with variably defined margins, projections wit scalloping between roots. -txmnt: surgical exploration. II. Giant cell lesions A. Central giant cell granuloma: -clinical: painless expansion. -radiographic appearance: well-delineated, uni or multilocular RL. It usually xes the midline. -txmnt: curettage, 15-20% recurrence (must rule out HPT brown tumor) B. Cherubism: -clinical: bilaterally enlarged mand &/or max, eyes upturned toward heaven, failure of teeth to erupt. -radiographic appearance: unilocular or more commonly multilocular bilateral expansile RLs with multiple unerupted teeth. -txmnt: none---lesions usually burn out after puberty. C. Aneurysmal bone cyst: -clinical: facial swelling with rapid onset and possible pain -radiographic appearance: uni- to multilocular RL with marked cortical expansion and thinning (ballooning or blown-out distension). -txmnt: curettage, but 50% recur requiring more aggressive surgical txmnt. III. Benign Fibro-Osseous lesions A. Fibrous dysplasia: 2-types: Monostotic (0-20y) & Polyostotic (less than 30y) -clinical: painless slow-growing bone swelling. -McCune-Albrights syndrome: caf-au-lait spots, endocrine Disturbances (early occurring puberty) -pathologic fracture (hockey-stick deformity) -radiographic appearance: diffuse ground-glass, orange peel radiopacity. -txmnt: excision of smaller lesions or cosmetic re-contouring. No radiation therapy.
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B. Periapical cemental dysplasia: -clinical: blacks more common than whites/teeth are vital. -radiographic appearance: -early: circumscribed periapical RL -mid-late: progressive calcification surrounded by a RL rim. -txmnt: none C. Focal cemento-osseous dysplasia: -clinical: white more common than blacks. -radiographic appearance: well defined mixed lesion with irregular borders -txmnt: periodic observation. D. Florid cemento-osseous dysplasia: -clinical: blacks more common than whites; poss dull pain, expansion, or fistula formation---may see exposure of yellowish avascular bone-like material. -radiographic appearance: multiple lobular radiopaque lesions. -txmnt: good OH to prevent perio disease. E. Ossifying fibroma: -clinical: painless swelling -radiographic appearance: well defined unilocular mixed lesion, usually with a sclerotic border and may see downward bowing of the inferior border of the mandible -txmnt: enucleation of tumor mass F. Juvenile ossifying fibroma: -clinical: may see rapid growth along with: exophthalamus, proptosis, & nasal obstruction. -radiographic appearance: mixed lesion with fairly well defined borders. -txmnt: small and slow excision. IV. Benign neoplasms A. Osteoma: -clinical: 2-types---periosteal osteomas (on surface of craniofacial bone) & endosteal osteomas (within medullary cavity). -radiographic appearance: circumscribed sclerotic mass -txmnt: rule out Gardners syndrome, but excision is txmnt. B. Osteoid osteoma: -clinical: pain most common at night and relieved by aspirin. -radiographic appearance: will circumscribed RL defect surrounded by dense sclerotic bone. -txmnt: complete excision or will get recurrence. C. Osteoblastoma: -clinical: pain, dull and achy, NOT relieved by aspirin and less often nocturnal. -radiographic appearance: 2-10cm in diam. May look like osteosarcoma due to sunburst pattern. -txmnt: conservative complete excision. D. Cementoblastoma: -clinical: slow growing with poss expansion.

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-radiographic appearance: calcified mass intimately Assoc with the root, but root outlines obscured usually surrounded by a RL rim. -txmnt: excision. V. Malignant Neoplasms of Bone A. Osteosarcoma: An osteoid producing neoplasm from bone---2nd most common malignancy. -clinical: painful swelling, loose teeth, paresthesia, nasal obstruction, epistaxis, pathologic fractures, & ulceration over the lesion. -radiographic appearance: mixed lesion, aggressive expansion, bone above normal height, symmetrical widening of the PDL, sunburst pattern in 25% of cases. -lab findings: elevated serum alkaline phosphatase. -txmnt: radical resection w/ chemo, radiation, or both. B. Chondrosarcoma: A non-osteoid producing malignancy---3rd most common malignancy. -clinical: painless swelling and loosening of teeth. -radiographic appearance: sunburst appearance like osteosarc, but more cotton wool-like -txmnt: radical resection, chemo and radiation is NOT effective. 50% 5-yr survival if dx w/in 6mos. 0% survival if dx after 1-year. C. Fibrosarcoma: A collagen producing tumor; no osteoid or cartilage---the least common malignancy. -clinical: painful swelling, loose teeth, paresthesia, firm but not bone hard. -radiographic appearance: RL process with aggressive resorption. -txmnt: radical resection with chemo. D. Ewings Sarcoma: -Probably neuroectodermal---4th most common malignancy. -clinical: intermittent pain with swelling most common, fever, anemia, & leukocytosis. -radiographic appearance: primarily RL with onion skinning. -txmnt: a combo of surgery, radiation and aggressive chemo. E. Multiple Myeloma: -50% of all primary bone malignancies, clonal plasma cell differentiation. -clinical: anemia, bone pain, infection, renal insufficiency, pathologic fractures, & amyloidosis. -radiographic appearance: multiple punched-out radiolucencies, soapbubble appearance. -lab findings: normocytic anemia, myeloma protein: IgG-60%, IgA-25% Bence-Jones proteins in urine. -txmnt: chemo and adrenocorticosteroids. VI. Review A. Common in the mandible: 1. Acute & chronic osteomyelitis 2. ORN
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3. Langerhans cell disease 4. Simple bone cyst 5. Central giant cell granuloma 6. Cherubism 7. Aneurysmal bone cyst 8. Periapical cemental dysplasia 9. Focal cemento osseous dysplasia 10. Ossifying fibroma 11. Osteoid osteoma 12. Osteoblastoma 13. Cementoblastoma B. Common in the maxilla: 1. Pagets disease 2. Fibrous dysplasia (monostotic & polyostotic) 3. Juvenile ossifying fibroma C. More common in males: 1. Acute osteomyelitis 2. Chronic osteomyelitis 3. Pagets disease 4. Langerhans cell disease 5. Osteoid osteoma 6. Osteoblastoma D. More common in females 1. Central giant cell granuloma 2. Aneurysmal bone cyst 3. Periapical cemental dysplasia 4. Focal cemento osseous dysplasia 5. Florid cemento osseous dysplasia 6. Ossifying fibroma 7. Juvenile ossifying fibroma E. Sunburst appearance on radiographs: 1. Osteosarcoma 2. Chondrosarcoma 3. Osteoblastoma F. Onion skinning appearance on radiographs: 1. Ewings sarcoma 2. Chronic osteomyelitis G. Ground glass (orange peel) appearance: 1. Fibrous dysplasia 2. HPT Allergic, Immunologic, & Dermatologic Diseases I. Recurrent aphthous stomatitis -Numerous theories to the cause:
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-allergies -genetic predisposition -hematologic abnormalities -hormonal influences -infectious agents -nutritional imbalances -stress or trauma -lesions are limited to non-keratinized mucosa A. Minor aphthous ulcerations (80%): -begins as a red macule. -develops in a 3-10mm ulceration. -removable membrane w/ erythematous halo. -heals in 7-14 days w/out scarring. B. Major aphthous ulcerations: -these are deeper than the minor type. -they are 1-3cm in diameter. -heal in 2-6 weeks with possible scarring. C. Herpetiform aphthous ulcerations: -these are the greatest # of lesions and recurrences. -these clinically look similar to primary HSV. -** any mucosal surface may be involved. -txmnt: topical and systemic corticosteroids. II. White sponge nevus (familial epithelial hyperplasia) -clinical: white, rough, surface lesion due to epith thickening---bilateral on buccal mucosa. Could mimic cheek biting or squamous cell carcinoma. -txmnt: none

III. Darriers disease (keratosis follicularis) -a defect in the adhesion of epithelial cells. -clinical: looks like papillary hyperplasia or nicotine stomatitis. On skin, see numerous red, pruritic papules. A foul odor can be a problem. -txmnt: sunscreen & retinoids IV. Epidermolysis bullosa -3 broad categories: simplex, junctional, & dystrophic -junctional: often death at birth. -dystrophic: type were most often concerned with. -oral mucosa most often involved in this form. -subepithelial separation due to defective anchoring filaments. -** a pre-disposition to sq. cell ca. -scar formation causes limited movement. -assoc. dental abnormalities: anadontia, enamel hypoplasia, neonatal teeth, severe caries. -txmnt: supportive, no cure.
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V. Pemphigus vulgaris -most common type of pemphigus. -initial lesion is a vesicle or bulla. -these blisters are very fragile and quickly rupture forming painful ulcers & heal slowly. -see Nikolskys sign: -rubbing or blowing air on uninvolved mucosa creates a blister. -this sign may also be present in cicatricial pemphigoid and rarely in lichen planus. -histo: -row of tombstones on basement membrane (left behind after epith splits off). -Tzanck cells: acantholytic epithelial cells with enlarged dark nuclei. -direct immunofluorescence: IgG & IgM autoantibodies. -txmnt: aggressive corticosteroids. Usually fatal w/out txmnt. VI. Cicatricial Pemphigoid (BMMP) -these are autoantibodies formed against a component of the basement membrane -clinical: vesicles and ulcers that may heal with scarring (oral mucosa often does not scar). Nikolskys sign may be present. Gingiva is almost always involved with diffuse erythema. It may also involve the skin, conjunctiva of the eye, nose, pharynx, esophagus, & larynx. -ocular involvement: subconjunctival fibrosis, adhesions---scarring may cause blindness. -histo: see continuous linear band of IgG & C3. -txmnt: topical &/or systemic corticosteroids; ophthalmologic consult. VII. Erythema Multiforme -3 predisposing factors: 1. Drugs (esp. sulfa drugs) 2. Vaccinations 3. Viral infections (esp. herpes simplex) -Skin lesions mainly on extremities and face---target lesions. -Oral lesions: painful vesicles and ulcers; buccal mucosa and crusting of lips. -txmnt: remove causative drugs, if any. Can use topical and systemic corticosteroids. -Most important complication of EM = dehydration. -2 subsets of EM: 1. Stevens-Johnson syndrome: -more severe form of EM -lesions on skin, oral mucosa, conjunctiva & genitals 2. Toxic Epidermal Necrolysis (TEN) -the most severe form of EM -female predominance -34% mortality rate -tx in hospital burn unit VIII. Lichen Planus -Cytotoxic cell-mediated hypersensitivity. -lesions found on legs: purple, pruritic, polygonal papules. -intraorally: lace-like network of white lines called Wickhams striae.
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-commonly on buccal mucosa, oral candidiasis may accompany LP. -2 types of LP: 1. Reticular LP (the most common) -asymptomatic, white lesions due to epithelial thickening (Wickhams striae) 2. Erosive LP -painful ulcers, erythematous gingiva. -histo: 1. Degeneration of basal cell layer 2. Hyperkeratosis 3. Band-like lymphocytic infiltration adjacent to epithelium 4. Saw-tooth rete ridges 5. Civatte bodies -txmnt: -if asymptomatic, no txmnt needed -if symptomatic, topical of systemic corticosteroids -immunofluorescence patterns: 1. Lichen planus: shaggy 2. Cicatricial pemphigoid: linear 3. Pemphigus vulgaris: fishnet pattern Rx for LP: 1. Rx: 0.2% Triamcinalone (oral suspension) Disp: two 40mg vials 2. Rx: Lidex (fluocinide) ointment 0.05% with Orabase, 15g Sig: apply PRN

3. Rx: Prednisone 20mg Disp: 50 tabs Sig: take 3-4 tabs q.d. for 10-14 days, then 1 tab q.d. for up to 14 days. 4. Rx: Triamcinalone acetonide (Kenalog) in Orabase (0.1%) Disp: 1 tube Sig: apply t.i.d. over the lesion 5. Rx: Dexamethasone (Decadron) elixir 0.5%mg/5ml Disp: 100ml Sig: rinse with 1 teaspoon (5ml) for 5 min. and expectorate. Use q.i.d. -Lichen planus can be associated with Hep C? Viral antigens, viral induced cytokines. IX. Lupus Erythematosus -An autoimmune disease with 2 types: Chronic cutaneous lupus erythematosus (CCLE) & Systemic lupus erythematosus. A. CCLE: -affects only mucosa and skin
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-the mucosal lesions consist of red patches, painful ulcers, & white epithelial thickening. -most common oral manifestation of lupus is candidiasis. -most common lesion on face is the butterfly rash. This becomes worse if exposed to sunlight. B. SLE: -serious multi-system disorder -antibodies are formed against cells and tissues. -the skin and oral mucosal lesions are similar to those of CCLE. -signs and symptoms: -fever -arthritis -kidney disease (what kills these patients) ** -CNS disease -heart disease (Libman-Sacks endocarditis)---antibiotic prophylaxis recommended if this exists. -lab findings: elevated ANA -txmnt: immunosuppressants, avoid sunlight. X. Systemic sclerosis -An abundance of dense collagen deposited in all tissues. -4 clinical features: 1. Raynauds phenomenon (hands become a shade of white, then blue and painful) 2. Mask-like face 3. Microstomia (purse-string mouth) 4. Short/claw-like fingers (puffy sausage look leads to this) -fibrosis leads to organ failure---lungs, hear & kidneys -This is a CREST syndrome: C-calcinosis cutis R-Raynauds E-Esophageal constriction S-sclerodactaly T-telangiectasias -On radiographs, see widened PDL. XI. Angioedema (angioneurotic edema) -Diffuse rapid swelling of soft tissues. -Sites include the face, hands, arms, legs, respiratory & GI tracts. -Itching and erythema are common, but pain is unusual. -Swelling usually subsides w/in 24-hrs. -txmnt: 1. acute: antihistamines, IM epi, IV corticosteroids/intubation 2. chronic: prophylaxis; medications to induce production of C1-INH XII. Contact stomatitis

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-Numerous foods and dental materials have been implicated here (chewing gums, dentrifices, and mouthwashes). Also, topical anesthetics, restorative materials, denture acrylic, impression materials & denture adhesives can cause contact stomatitis. -Why is oral mucosa less sensitive than skin? 3 reasons: 1. salivary dilution 2. brief contact period 3. vascularity of the mucosa allows rapid resorption and dispersal of antigens. -Plasma cell gingivitis: clinically diffuse erythema and edema of gingiva and hyperkeratosis of the tongue. Ex: cinnamon flavoring -txmnt: removal of antigen, antihistamine (Benadryl), topical anesthetics and steroids. Benign & Malignant Epithelial Lesions I. Squamous Papilloma -Etiologically related to human papilloma virus (HPV types 6 & 11). -Soft, painless, & usually pedunculated with papillary or verrucoid (cauliflower) surface. -txmnt: conservative surgical excision; no association with malignant transformation. II. Verruca Vulgaris -Virally induced squamous proliferation (HPV types 2,4, & 40). -** This is contagious and can spread via autoinoculation (Ex: tips of fingers to fingers in mouth). -More common on skin, but does affect oral mucosa (less common in mouth). Often seen in children. -txmnt: conservative surgical excision. III. Condyloma Acuminatum (Venereal Wart) -Virally induced (HPV types 6,11,16, & 18), sexually transmitted and contagious through direct sexual contact> -These are sessile, pink, and larger than papillomas, often multiple and clustered. -txmnt: conservative surgical excision. IV. Focal Epithelial Hyperplasia (Hecks Disease) -Virally induced (HPV types 13 & 32). -Usually seen in childhood, affects labial, buccal, and lingual mucosa most often. -Lesions are small, discrete, often clustered and may have many papillary or cobblestone surface texture. -txmnt: conservative surgical excision, but spontaneous regression may occur. V. Verruciform Xanthoma -Occurs in adults. -Appears as soft, sessile elevated white, yellow-white or red mass with verruciform surface. -Xanthoma cells are foamy looking. -txmnt: conservative surgical excision.

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VI. Inflammatory Papillary Hyperplasia -A reactive proliferation related to 3 things: 1. an ill-fitting denture 2. poor denture hygiene 3. prolonged wearing of denture -Usually seen on the hard palate, sometimes the mandibular alveolar ridge. -txmnt: removal of denture may help, but excise chronic lesions. VII. Nicotine Stomatitis (smokers palate) -Associated with long-term use of pipe smoking (may even see with cigarette smoking). -The mucosa is diffusely white or gray with numerous elevated papules with red centers (these represent inflamed salivary gland duct orifices). -Reversible: can see improvement after about 2-weeks of cessation). -This is not usually preneoplastic, but if it persists, consider it to be leukoplakia. VIII. Keratoacanthoma (self-healing carcinoma) -This is a superficial invasive sq. cell ca. -Its a self-limiting epithelial proliferation with clinical & histological similarities to SCC. -2 heredity forms include Muir-Torre syndrome & Ferguson Smith type -Muir-Torre: sebaceous neoplasms, keratoacanthomas, and GI carcinomas. -Ferguson Smith: occur by themselves in early life. -etiology: sun damage. -95% of lesions occur in older adults on the outer edge of the vermilion border of the upper and lower lip---intraoral occurrence is extremely rare. -Lesions may regress spontaneously w/in 6-12 months, leaving a depressed scar. -txmnt: surgical excision. IX. Actinic Keratosis & Actinic Cheilosis -Preventable with adequate sun protection. -These are pre-malignant skin or lip lesions caused by UV light, especially in fair-skinned people. -See scaly, white, gray, or brown plaques. -Early changes show blurring of the zone b/w vermilion border and skin of lip. -txmnt: excision---vermilionectomy is often performed (a lip shave). X. Smokeless Tobacco Keratosis -See in anterior labial vestibule (snuff) and buccal mucosa (chewing). -See slightly elevated leukoplakia, gingival recession, loss of frontal plate of bone, & occlusal wear from abrasion. XI. Leukoplakia -NOT A DIAGNOSIS---JUST A DESCRIPTIVE CLINICAL TERM -Its white patch or plaque that cannot be characterized clinically or pathologically as any other disease. -Some are pre-malignant or malignant lesions. -Causes of leukoplakia: 1. Lichen planus
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2. 3. 4. 5. 6. 7. 8.

Friction keratosis Factitial injury Smokeless tobacco Nicotine stomatitis White sponge nevus Leukoedema Oral cancer & epithelial dysplasia

XII. Leukoplakia -90% of those that occur show dysplasia or carcinoma occur on the tongue, vermilion border of the lip, and the floor of the mouth. -Leukoplakia caries the greatest risk of being dysplastic on the tongue & floor of the mouth (lateral tongue = 25%, floor of mouth = 45%). -85% of oral cancers are clinically leukoplakias. -Typical presentation = male (70%), average age = 60. XIII. Verrucous Carcinoma -Female predilection: 4:1 -Associated with smokeless tobacco. -Clinically large, broad based, papillary (cauliflower-like) leukoplakia lesion. -Very well differentiated form of oral cancer. -txmnt: complete surgical excision---radiation is contraindicated. IX. Oral Cancer -8 signs of oral cancer: 1. A lump or thickening in mucosa, gland, or lymph node area. 2. An ulcer that doesnt heal. 3. Abnormal bleeding or discharge. 4. Pain or numbness. 5. Persistent cough or hoarseness. 6. Any change in a mole on the skin. 7. Any change in bowel or bladder habits. 8. Persistent indigestion or dysphagia. -8 predisposing factors to oral cancer: 1. Tobacco use 2. Alcohol use 3. Radiation 4. Chronic irritation 5. Vitamin deficiency 6. Oncogenic viruses 7. Immunocompromised patients 8. Plummer Vinson syndrome -Alcohol and tobacco appear to have a synergistic effect, each making the other more dangerous. -A combined use risk is 15x that of the non-user. -Radiation, chiefly UV wavelengths, affect lower lip.
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-Main viral threat is from HPV types 16,18,31, & 33. -Types of oral cancer: 1. Squamous cell carcinoma (90%) 2. Everything else (10%) a. salivary gland adenocarcinoma b. metastatic tumors c. sarcoma d. melanoma e. lymphoma -Typical high risk patient: 1. male 2. over 40 years old 3. tobacco &/or alcohol user 4. malnourished 5. immunocompromised 6. chronic irritation -High risk sites: 1. lower lip (90%) 2. lateral or ventral tongue (50%) 3. FOM (30%) 4. Soft palate (10%) -Distribution of oral cancer 1. Lip cancer a. 90% occur on lower lip b. predominantly middle aged males c. loss of vermilion architecture d. pipe smokers are at increased risk e. metastasis is late in the course of the disease f. 90% 5-year survival 2. Tongue cancer a. approximately 50% of all intra-oral cancer -lateral & ventral surfaces are common -dorsum is rare ** b. 75% male c. tobacco and alcohol abuse associated d. the worse prognosis is more posterior 3. Floor of mouth cancer a. approximately 30% of all intra-oral cancers b. 90% males c. tobacco & alcohol abuse associated d. 67% 5-year survival if localized; 20% 5-year survival if metastasis to cervical lymph nodes has occurred. 4. Gingival cancer (rare) a. less than 10% of all intra-oral cancers b. male predilection c. the mandible is favored d. early bone invasion
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e. 33-50% show lymph node metastasis on initial presentation f. 40% 5-year survival if localized; 10% 5-year survival if metastatic. 5. Palatal cancer a. approximately 10% of all intra-oral cancers b. soft palate lesions are more common than hard palate lesions c. sq. cell ca. & melanoma: middle aged males d. salivary (MEC, PLGA): increasingly female population e. SCC: 70% 5-year survival if localized; 15% 5-year survival if metastasis occurs. -Cancer txmnt: 1. Surgery (controversy: resection, then follow with radiation---or---initial radiation to shrink tumor, then resect, but run risk of brittle vessels and impaired healing at surgery) 2. Radiation therapy: a. 4 cellular effects: -toxic metabolic breakdown products -inactivation of enzyme systems -coagulation of protoplasmic colloids -denaturation of nuclear proteins b. 3 clinical effects: -epithelial atrophy -xerostomia and caries -vascular thrombi and bone infarction (ORN): low risk of ORN under 45Gy (4500cGy or rads); almost certain risk of ORN over 65Gy (6500cGy or rads) 3. Chemotherapy a. Objective: to simultaneously destroy all malignant cells by attacking cancer with several different drugs, each affecting a different stage of cell reproductive cycle. b. Classification of chemotherapeutic agents: -Antimetabolites -Alkylating agents -Antibiotics -Vinca alkaloids -Other agents c. Pathologic effects of chemotherapy -large painful ulcers -marrow suppression (thrombocytopenia & agranulocytosis) -opportunistic infection (herpes & candida) -Histopathologic grading of sq. cell ca. -well differentiated -moderately differentiated -poorly differentiated -** Clinical staging is of greater importance than histopathologic grading when predicting biologic outcome.

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Malignant Soft Tissue Tumors -Carcinomas arise from malignant soft tissues of epithelial origin. -Sarcoma arise from malignant soft tissues of mesenchymal origins. -Sarcomas are relatively rare compared to carcinomas and most sarcomas do not arise from malignant transformation of a benign counterpart. I. Fibrous Tissue A. Fibrosarcoma -Malignant neoplasm of fibrous C.T. origin. -Capable of distant metastasis. II. Neural Tissue A. Neurogenic sarcoma (malignant schwannoma) -Develops from either a neurofibroma or de nova. III. Muscle Tissue A. Rhabdomyosarcoma -** Most common soft tissue sarcoma of children & young adults. -Male predilection -txmnt: radical surgical excision, radiation, or chemo. B. Leiomyosarcoma IV. Vascular Malignancies A. Hemangiopericytoma B. Kaposis sarcomas (Angiosarcoma): involves lymph vessels, arteries, capillaries, & veins. V. Adipose Tissue Malignancy A. Liposarcoma: malignant tumor of adipose tissue. Soft Tissue Neoplasms I. Inflammatory Papillary Hyperplasia -A reactive process due to: 1. poor fitting denture 2. wearing denture 24 hrs. a day 3. candida albicans -Clinically: see numerous red, edematous, papillary projections on the hard palate. -Txmnt: 1. discontinue wearing denture 24 hrs. a day 2. prescribe antifungal medication if candidosis is present. 3. excise lesion or construct new denture II. Inflammatory Fibrous Hyperplasia (Epulis Fissuratum) -Usually denture induced caused by irritation of the denture. -Clinically: see rolls of tissue associated with a denture flange. -Txmnt: excise lesion, remake or reline denture.

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III. Peripheral Ossifying Fibroma (POF) -A gum bump. -Young adults (less than 30 yrs. old) with a female predilection. -** Seen exclusively on the gingiva. Its exophytic, sessile, firm. -Origin: PDL -This is the only gum bump thats most likely to be normal in color and firm. IV. Giant Cell Fibroma -Teenagers and young adults (less than 20 yrs. old) -3 common sites: gingiva, tongue, or palate -When on gingiva, its usually seen behind teeth #s 22 & 27 (retro-cuspid of Hershfield). -Txmnt: excisional biopsy (no recurrence). V. Fibroma -Clinically: firm, asymptomatic nodule---very common. -Common locations: buccal mucosa & lower lip. -It represents hyperplastic fibrous tissue

VI. Non-specific Hyperplastic Gingivitis -Focal enlargement of gingiva---especially inter-dentally. -Clinically: see erythematous, boggy, ulceration with dental plaque, calculus, & pocket formation. VII. Gingival Hyperplasia Secondary to Medications -3 possible etiologies: 1. Phenytoin (Dilantin): an anticonvulsant drug 2. Cyclosporine A: an immunosuppressive drug 3. Calcium Channel Blockers: Ex: Procardia -These drugs cause fibrous hyperplasia, but the mechanism is not understood. -The gingiva are enlarged, firm to palpation, non-tender, and usually do not bleed. -The crowns of the teeth may be partially or totally covered by the gingival over-growth. VIII. Hereditary Gingival Fibromatosis -Idiopathic fibrous hyperplasia of the gingiva. -Clinically: the tissue is of normal color or may be paler. The overgrowth may prevent eruption of teeth. IX. Muscle Tissue A. Leiomyoma -benign tumor of smooth muscle -see in middle aged adults -clinically: see on tongue, hard palate, & buccal mucosa as a slow growing nodule that may be painful. B. Rhabdomyoma -benign tumor of skeletal muscle
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-seen in adults greater than 40 years old -clinically: see on tongue and the FOM as a well-circumscribed mass. X. Fat tissue A. Lipoma -see in adults -clinically: see on buccal mucosa, tongue, and the FOM as a sessile or pedunculated yellow nodule, soft to palpation. XI. Neural Tissues A. Neurofibroma -originates from neural tissues: Schwann cell or perineural fibroblasts. -see in young adults -clinically: see on tongue and other oral mucosa as a sessile or pedunculated smooth-surfaced nodule. -** They may be as multiple as a manifestation of neurofibromatosis. B. Neurofibromatosis (von Recklinghausens Disease) -autosomal dominant -see caf-au-lait spots -can see pigmented nodules of the iris (Lisch nodules) -skeletal abnormalities (macrocephaly), bone cysts, & craniofacial asymmetry. C. Neurilemona (Schwannoma) -originates from schwann cell -clinically: see raised nodule thats freely movable. -see Antoni A (organized spindle cells) & Antoni B tissue (spindle cells haphazardly arranged) D. Traumatic Neuroma -cause: trauma to peripheral nerve -painful; especially if associated with a denture against the mental foramen. E. Multiple Endocrine Neoplasia (MEN III) 1. medullary carcinoma of the thyroid -can metastasize and cause death 2. pheochromocytoma of the adrenal medulla -benign neoplasm of chromaffin cells -can result in HTN 3. mucosal neuromas -appear early in life and may be the 1st sign of the syndrome F. Granular cell tumor -benign tumor of neural (schwann cell) or undifferentiated mesenchymal cells. -clinically: see a raised nodule with normal or white surface---may feel indurated. -psudoepitheliomatous hyperplasia XII. Vascular Tissues A. Hemangioma
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-see at birth and childhood -female predilection -site: lips, tongue, & buccal mucosa -clinically: see flat or raised, red or blue color; may be ulcerated -types: capillary hemangioma and cavernous hemangioma -txmnt: none XIII. Vascular Malformation A. Arteriovenous (AV) malformation -abnormal vessel formation causing dilatation of arteries, veins, & capillaries -clinically: usually present at birth and grows with the patient. It does not involute and may produce a thrill or bruit. -total surgical removal is often not possible; surgical hemorrhage can be a problem. B. Sturge-Weber Syndrome (Encephalotrigeminal Angiomatosis) -vascular malformations of cerebral meninges causing neurologic problems such as mental retardation, hemiparesis, & seizures. -the vascular malformations are commonly termed port wine stains -this follows the distribution of the trigeminal nerve (V1, V2, & V3) C. Lymphangioma -can see at birth and/or childhood -affected sites are tongue, lips & neck (cystic hygroma)---deeper lesions may cause macroglossia or macrocheilia D. Pyogenic granuloma -female predilection---common in pregnant females -most commonly found on the gingiva. -clinically: see an overgrowth of granulation tissue secondary to irritation. E. Peripheral ossifying fibroma (POF) -seen in young adults with a female predilection -** seen exclusively on the gingiva -originates in PDL F. Peripheral giant cell granuloma (PGCG) -female predilection -exclusively on gingiva or edentulous alveolar ridge -clinically: see exophytic, sessile, red, blue, or purple color -possibly periosteal origin G. Congenital epulis of the newborn -uncertain origin -site: gingiva; maxilla 2:1 (alveolar ridge) -clinically: pedunculated lesion, may grow quite large H. Kaposis sarcoma -a vascular cancer thats common in AIDS patients -It can be a surface lesion or a soft tissue enlargement I. Hematoma -a subepithelial blood blister J. Extravasated blood
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-occurs due to the presence of blood outside of a blood vessel -these lesions do not blanch upon pressure; theres often a hx of injury or a bleeding problem K. Hemangiopericytoma -originates from pericytes -has benign, borderline, & malignant forms -usually deep seated in muscle L. Myxoma -this is the soft tissue, non-odontogenic myxoma -its diffuse and poorly circumscribed

Odontogenesis, Odontogenic Cysts, & Odontogenic Tumors I. Odontogenesis -The first signs of tooth development take place around embryonic day 37 (6th week of fetal life) with the budding of the epithelium from the crest of the future alveolar ridge. -Development of the entire primary dentition (20 teeth) is initiated b/w the 6th & 8th week of embryonic development. -Succedaneous teeth (20 teeth) begin development b/w the 20th week in utero & the 10th month after birth; the permanent molars (12 teeth) follow. -The stages: 1. The bud stage: -epithelial cells from the dental lamina bud off and begin forming the dental enamel organ for each primary & succedaneous tooth. 2. The cap stage: -continued proliferation of the epithelium into the ectomesenchyme with the formation of the dental papilla and follicle. -the dental papilla is the formative organ of dentin and pulp. -dental papilla + dental follicle + dental organ = tooth germ 3. Bell stage: -tooth germ becomes separated from the oral epithelium -differentiation into 4 components: inner enamel epithelium, outer enamel epithelium, stellate reticulum, & stratum intermedium) -the inner enamel epithelium assumes the dominant inductive role. 4. Crown stage: -the inner enamel epithelium induces the odontoblasts of the dental papilla to lay down dentin. -ameloblasts can now secrete the enamel matrix -as enamel matrix is laid down, the stellate reticulum collapses and the odontogenic epithelium is referred to as the reduced enamel epithelium -inner & outer enamel epithelium continue to proliferate in an apical direction to form Hertwigs epithelial root sheath and the remnants of this root sheath persist within the PDL space as the rests of Malassez

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II. Odontogenic Cysts -By definition, an odontogenic cyst is a pathologic cavity in bone or soft tissue, which is lined by epithelium of odontogenic origin. This epithelial lining may be derived from the dental lamina, dental organ, reduced enamel epithelium, or rests of Malassez. -2 classifications: inflammatory & developmental A. Inflammatory odontogenic cysts 1. Apical periodontal cyst -the most common of all odontogenic cysts -infection, inflammation, or pulpal necrosis are responsible for its origin. -always assoc. with a non-vital tooth -symptoms may include pain, swelling, drainage, and tooth mobility. -origin: Hertwigs epithelial root sheath -txmnt: endo or extraction with curettage of the socket 2. Residual cyst -a cyst that persists following the extraction of a tooth -origin: may have originally been an apical periodontal cyst, periapical granuloma, or a dentigerous cyst -txmnt: surgical exploration and thorough curettage 3. Paradental cyst (Buccal bifurcation cyst) -origin: reduced enamel epithelium -presents as a buccal swelling adjacent to a molar tooth (mand 1st molar most common in children, mand 3rd molar most common in adult). -assoc. with an enamel projection in the area of root bifurcation -occl radiograph will show lingual displacement of the tooth -txmnt: soft tissue curettage with perio f/u or extr of tooth B. Developmental odontogenic cysts 1. Dentigerous cyst -the most common developmental cyst -always assoc. with the crown of an unerupted tooth (usually a 3rd molar) -can cause root resorption, tooth displacement, and pain -on radiograph, see a well demarcated unilocular RL, surrounding the crown of an impacted tooth. -histo: an empty or clear fluid filled cyst, which is lined by thin nonkeratinized epith. -txmnt: extr with curettage or marsupialization. -rare malignant transformation, can develop into an ameloblastoma 2. Eruption cyst -a variant of the dentigerous cyst caused by fluid or blood b/w the crown of an erupting tooth and the surface mucosa. -lesions appear as bluish-purple, dome-shaped swellings at the crest of the alveolar bone. -txmnt: none required 3. Lateral periodontal cyst
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4.

5.

6.

7.

-origin: post-functional dental lamina or rests of Malassez -a lesion of adulthood---avg. age = 50 -most common location: mand PM/canine area (67%); max lateral (33%). Adjacent teeth are vital. -radiograph reveals a well-circumscribed unilocular mid-root RL -txmnt: conservative surgical excision/preserve adjacent tooth structure -multilocular-variant is termed botryoid (grape-like) odontogenic cyst Gingival cyst of infancy and gingival cyst of adult -origin: post-functional dental lamina rests -childhood lesions appear as multiple smooth white nodules on the alveolar ridge, often present at birth. Do not confuse with Epsteins Pearls (midline of hard palate) or Bohns nodules (hard/soft palate junction). -the cysts are filled with keratin debris -txmnt: none required -some pathologists consider the adult lesion to be the soft tissue counterpart of the lateral periodontal cyst. Odontogenic keratocyst (OKC) -the most common multilocular radiolucency; they may displace teeth, cause root resorption, thin the bony cortex, and on rare occasions, perforate the cortical bone. -Peak incidence: 3rd-4th decade of life (male predilection) -mandible affected 2x as often as maxilla---with the angle & 3rd molar area being the most common sites. -25% will be multilocular, and about 40% will be assoc. with an impacted tooth. -histo: a. corrugated (wavy) keratin lining b. keratin is parakeratin c. 6-10 cell layers thick d. basal cell layer exhibits palisades (like a picket fence) e. basal cell layers are dark (hyperchromatic nuclei) -OKC is a major component of the Nevoid Basal Cell Carcinoma -txmnt: from enucleation with curettage to en bloc resection Keratinizing odontogenic cyst (KOC) -originally described as the orthokeratinized variant of the OKC -almost always presents as a unilocular RL assoc. w/ an impacted 3rd molar -no hyperchromatism or palisaded arrangement of cells. Calcifying odontogenic cyst (Gorlin cyst) -expansile intraosseous lesion -bi-modal peak incidence: 2nd & 7th decades of life -see radiopaque flecks, masses or tooth-like densities -** this is the only odontogenic cyst with radiopacities as a component
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-ghost cells in epithelial lining -txmnt: surgical excision -the aggressive non-cystic variant is the epithelial odontogenic ghost cell tumor (seen in odontogenic tumor section) 8. Glandular odontogenic cyst -called this b/c of duct-like structures w/in the wall 9. Carcinoma arising in an odontogenic cyst -rare event; most are sq. cell carcinomas -see ragged, irregular borders which may be the clue to malignancy III. Odontogenic Tumors -All result from some manner of mis-directed odontogenesis. -Most often classified based on the tissues from which they are derived (epithelial, mesenchymal, or both). A. Epithelial origin 1. Ameloblastoma -the most common epithelial odontogenic tumor and most clinically significant benign odontogenic neoplasm -origin: remnants of the dental lamina -most common in the 3rd-4th decade of life (no gender pred.) -80% in mand.---molar & ascending ramus most common loc. -slow growing tumors; unlimited growth potential that can expand the bony cortex -tooth displacement, mobility, and root resorption are common -histo variants: a. follicular (most common) b. plexiform c. desmoplastic (fibro-osseous radiographic appearance) d. acanthomatous e. granular cell f. basal cell patterns -with the exception of the plexiform pattern, all exhibit the histologic features of ameloblastoma -the islands of neoplastic odontogenic epith are encircled by basaloid cells with hyperchromatic and palisading nuclei. The nuclei are polarized away from the basement membrane and exhibit subnuclear vacuolization of the cytoplasm. -can cross the midline of the face -txmnt: depends on the size of the lesion; the more radical the surgery, the lower the recurrence rate. Radiation is of little value. -variants of the ameloblastoma a. unicystic & plexiform unicystic: generally occur in younger individuals (teens & young adults), present in a dentigerous cyst-like manner b. peripheral: less than 1% of ameloblatomas---present as painless gingival nodules/no intrabony component

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c. ameloblastic carcinoma: occurs after several unsuccessful attempts at resection of a benign ameloblastoma d. metastatic ameloblastoma: benign in a distant location; lung is most common metastatic site 2. Calcifying epithelial odontogenic tumor (CEOT) -also known as the Pindborg Tumor -origin: stratum intermedium -usually in early adulthood (avg. age = 40) -most common location: mand PM/molar region -see calcifications on radiograph -often assoc. with unerupted tooth -amyloid can be seen in most tumors -less aggressive than the ameloblastoma -txmnt: surgical excision or en bloc resection 3. Squamous odontogenic tumor -see teeth floating in air (PDL space is not intact) -can see in post mand or ant max as a triangular RL -lesion can mimic juvenile perio or eosinophilic granuloma (Histiocytosis X) of bone 4. Epithelial odontogenic ghost cell tumor -the neoplastic or non-cystic variant of the Gorlin cyst. -seen in 4th or 5th decade of life 5. Clear cell odontogenic carcinoma -rare---1st described in 1985 -see painful bony swelling of either jaw B. Mesenchymal origin 1. Odontogenic fibroma (central odontogenic fibroma) -most common in females (young adult females) -maxilla is favored site -when affecting the ant max, it presents as a soft tissue cleft -see well defined RL often assoc. with the apical area of erupted teeth. -txmnt: adequate surgical removal 2. Odontogenic myxoma (most common) -origin: cells that would have formed the dental follicle -rare under age 10 and over age 50 -post mand is favored site of this honeycombed or multilocular tumor -can cross the midline -txmnt: wide local excision C. Epithelial and Mesenchymal 1. Ameloblastic fibroma -can turn into ameloblastic fibrosarcoma -usually assoc. with mand 1st molar (avg. age = 15) -txmnt: due to possible malignant transformation, curettage is inadequate, so conservative en bloc resection is recommended
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2. Ameloblastic fibrosarcoma -occurs in the 4th decade Ameloblastic fibro-odontoma -characterized by a rapid painful growth phase -txmnt: radical resection (50% recurrence rate) 3. Ameloblastic fibro-odontoma -clinical presentation similar to the ameloblastic fibroma -hard tissue takes form of haphazard attempts of tooth formation -occurs in slightly younger age group (10 yrs) -txmnt: conservative surgical excision 4. Odontoma -2 distinct forms: a. Complex -composed of normally appearing enamel, dentin, and pulp which are haphazardly arranged -usually in post mand b. Compound -looks like little toothlets, commonly b/w the roots of teeth in the ant max. -avg. age = 15 yrs with a male predilection -txmnt: conservative curettage 5. Adenomatoid odontogenic tumor (AOT) -slow growing & painless -known as the 2/3 tumor: -2/3 are female -2/3 are in the ant max -2/3 are assoc. with an impacted tooth (canine) -2/3 are under the age of 20 -the only odontogenic tumor with duct-like structures -txmnt: enucleation or curettage IV. Review of origins: -reduced enamel epith: -rest of Malassez: -dental lamina: -stratum intermedium: paradental cyst & dentigerous cyst lateral perio cyst, gingival cyst, squamous odontogenic tumor, & apical perio cyst ameloblastoma CEOT

Salivary Gland Pathology I. General Considerations A. Salivary gland functions: production of fluid that constitutes oral saliva 1. components: a. 99% water b. leukocytes c. desquamated epithelial cells d. bacteria---normal oral flora B. Function of saliva
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1. 2. 3. 4. 5. 6.

protection/lubrication buffer (6.0-7.4) taste & digestion antibody (IgA) enamel remineralization clotting time

II. Saliva A. Protection 1. The lubricant is glycoprotein 2. Mechanical washing of non-adherent bacteria B. Buffering capacity 1. Inhibition of bacterial colonization a. lysozyme can hydrolyze some bacterial cell walls b. lactoferrin binds free iron; depriving the bacteria 2. Minimizes acid production of plaque from sugar C. Taste & Digestion 1. recognition of noxious substances 2. minor role amylase breaks down starches 3. gusten protein for growth & development of taste buds D. Antibody 1. IgA capacity to clump/agglutinate microorganisms E. Enamel remineralization 1. high ionic concentration of calcium & phosphate ensures ionic exchange with the tooth surface, assisting in remineralization. F. Clotting time 1. decreased in experimental studies III. Salivary Gland Development -Formation begins with a solid cord of ectoderm & endoderm of cells from the epithelium of the stomodeum. -Central cells degenerate forming the lumen of the ductal system. -Terminal bulb epithelium maintains its 2 layers: inner & outer. -inner: acinar & intercalated duct cells -outer: myoepithelial cells -Development of parotid gland: 4-6wks of embryonic life -Development of submandibular gland: 6 weeks of embryonic life -Development of sublingual & minor glands: 8-12wks of embryonic life IV. Glandular Histologic Units A. Acinar units 1. Serous cells -pyramid shaped cell with rounded nuclei located at the basal 1/3 of the cell. -spherically arranged around the duct with the apex situated toward the lumen.
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-watery fluid 2. Mucous cells -pyramidal shaped with flattened nuclei, basally situated. -cytoplasm is clear & foamy -viscous fluid 3. Myoepithelial cells -features of epithelium & smooth muscles -contractile properties aid in secretion -spindle shaped cells with cellular processes B. Ductal system 1. Intercalated duct -intimately associated with acini -small diameter lined by short cuboidal epithelium 2. Striated duct -larger duct -columnar cells with central nuclei 3. Excretory duct -lining varies from pseudostratified epithelium near the striated duct to true stratified epithelium near the oral cavity V. Salivary Gland System -Major: parotid, submandibular, & sublingual -Minor: small aggregates of glands scattered throughout the oral cavity A. Parotid gland (largest) 1. develops from oral ectoderm 2. contents: almost exclusively serous 3. empties via Stensons duct 4. gland embraces the facial nerve B. Submandibular gland (submaxillary gland) (2nd largest) 1. develops from endoderm 2. contents: 80% serous; 20% mucinous 3. empties via Whartons duct C. Sublingual gland (smallest) 1. develops from endoderm 2. contents: 70% mucus secreting 3. empties via 2 ducts: Bartholins (largest) & Rivinus D. Minor glands -between 500 & 1,000 distinct glandular structures -location: buccal mucosa, lips, FOM, hard & soft palate, tonsillar pillars, and the tongue. -so, the anterior hard palate & gingiva do not have minor glands -Tongue: anterior ventral are Blandin & Nunn glands which are mucous posterior dorsal & ventral are von Ebner which are serous -Sebaceous glands are commonly found in normal oral mucosa (Fordyces granules) -minor glands on the palate secrete mostly mucous and the buccal mucosa, FOM, & lip predominantly secrete mucous & serous.
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VI. Clinical Features of Salivary Gland Tumors -Most common presentation: an asymptomatic swelling---whether benign or malignant. -Pain does not indicate malignancy. -Paresthesia is a sign of malignancy. -Facial nerve paralysis indicates a parotid malignancy 12-14% of the time. -if paresthesia, think Adenoid Cystic Carcinoma -Tumor growth rate is not a good indicator of benign or malignant -Tumor fixation or ulceration is a sign of possible malignancy VII. Surgical Treatment of Salivary Gland Tumors A. Parotid 1. Partial parotidectomy is minimal for benign & malignant tumors. 2. Superficial lobectomy is preferred for benign & low-grade malignant tumors of the superficial surface. 3. Total parotidectomy is txmnt for all high-grade malignant tumors, primary benign tumors of the deep lobe, recurrent benign or malignant parotid gland tumors (except Warthins tumor) B. Submandibular and Sublingual 1. Total submandibular gland removal for all tumors here. 2. Total sublingual gland removal for any tumor in this location. C. Minor glands 1. Wide local excision for all benign and low-grade malignancies -Radiation is contraindicated for any benign tumor. VIII. Benign Epithelial Neoplasms A. Mixed tumor (Pleomorphic adenoma) 1. Most common salivary gland neoplasm 2. Asymptomatic and slow growing 3. Female predilection 4. Called mixed tumor b/c it has mesenchymal-like formation & epithelium B. Myoepithelioma 1. 40% parotid, 21% in hard & soft palate 2. M=F 3. Average age = 44 C. Papillary cystadenoma lymphomatosum (Warthins Tumor) 1. 95% located in parotid 2. Predominantly male over 40 3. Associated with smoking 4. ** Most likely salivary gland tumor to be bilateral (10%) D. Basal cell adenoma 1. Most common in parotid 2. Asymptomatic swelling 3. Females more common/average age = 60 E. Canalicular adenoma 1. Most common site is upper lip
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2. Female predilection/average age = 65 3. May be multi-nodular

IX. Malignant Epithelial Salivary Gland Tumors A. Mucoepidermoid carcinoma 1. Most common salivary gland malignancy 2. 2nd most common salivary gland tumor 3. low-intermediate-high grades B. Acinic cell adenocarcinoma 1. 2nd most common salivary gland malignancy 2. most common gland is the parotid gland 3. Female predilection is 3:2 4. Slow growing C. Adenoid cystic carcinoma 1. Pain & paresthesia 25-33% of the time** 2. Most common in middle-aged years D. Polymorphous low grade adenocarcinoma 1. A minor gland tumor 2. Most common location = palate 3. Slow growing & painless 4. Female predominance E. Carcinoma-Ex-Mixed Tumor 1. Rapid growth after long indolent course 2. See pain, paresthesia, & fixation 3. 2 variants: a. carcinosarcoma -65% parotid; 22% submandibular -most patients over 50 yrs old -see swelling, pain, nerve palsy, & ulceration b. metastasizing mixed tumor -avg. age is 60 yrs old -can see a long interval b/w the primary tumor & metastasis (as long as 52 years) X. Non-Neoplastic Disorders of the Salivary Glands A. Obstructive disorders 1. Mucus escape reaction (mucocele) a. bluish/dome shaped swelling b. results from traumatic rupture of a duct c. txmnt: remove mucous sac & offending minor salivary gland 2. Mucus retention cyst a. epithelium lined cavity arising from salivary gland tissue b. most common in the parotid 3. Sialolithiasis

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a. deposition of calcium salts around nidus of debris within a duct lumen b. most common in submandibular gland c. episodic pain & swelling---esp. around meal times B. Idiopathic diseases 1. Necrotizing sialometaplasia a. most frequently affecting the posterior hard palate b. most common in adult males over 46 yrs c. initially see a painful, non-ulcerated swelling---within 2-3 wks, see a crater-like ulceration d. cc: My palate fell out 2. Benign cysts of the parotid a. lymphoepithelial cysts/branchial cleft cyst -can see in neck & oral cavity -developmental cyst of lateral neck---probably arises from entrapped salivary gland epithelium -located along anterior border of the SCM b. HIV assoc. sialadenopathy -can occur anytime during disease process -bilateral in about 60% of cases C. Autoimmune sialadenitis 1. Benign lymphoepithelial lesions a. BLEL or Mikuliczs disease -bilateral painless swelling of lacrimal & salivary glands -80% in women/mean age=50yrs -80% in parotid gland 2. Sjogrens syndrome a. chronic systemic autoimmune disorder b. 80% middle-aged females c. primary: sicca syndrome -keratoconjunctivitis -xerostomia d. secondary: assoc. with additional systemic disease -15% of people with RA have Sjogrens -30% of people with Lupus have Sjogrens XI. Incidence of Benign & Malignant Tumors Benign % -upper lip: 79% -parotid: 68% -submandibular: 60% -palate: 50% -lower lip: 40% -sublingual: 29% -tongue: 10% -FOM: 9% Malignant % 21% 32% 40% 50% 60% 71% 90% 91%
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-retromolar pad:

8%

92%

Oral Microbiology -Abscesses, cellulitis, & osteomyelitis are the most common mixed infections. -Pulpal & periapical infections are mostly streptococci (50%) & staphylococci (16%). -Anaerobes constitute about 25-50% of mixed infections. -Periodontal infections are alpha-hemolytic strep, mixed staph & strep, and most other members of oral flora. -Beta-hemolytic strep has groups A, B, C, F, & G -When you send an aspirate to the lab, you want them to ID the 3 most predominant species and a Kirby-Bauer susceptibility. -Group A Beta-hemolytic strep (S. pyogenes) is not viral & not flesh eating. I. Tuberculosis A. Pathogenesis 1. need 1-3 AFB in droplet reach the terminal air spaces 2. A positive smear & positive sputum means patient has disease 3. Must get patient into sputum (-) state b/f working on them B. Pulmonary TB 1. most common form of TB (82%) of cases 2. enter through lungs, then lymphatics (disseminated by blood) to from secondary sites of infection 3. signs: -low grade fever -night sweats -fatigue -weight loss -non-purulent cough C. Extra-pulmonary TB 1. usually in special populations (foreign born, HIV +) II. Cat Scratch Disease A. Clinical features 1. begins on skin 2. inoculation site is small (4-5mm papule) 3. spreads to regional lymph nodes B. Etiology 1. cat exposure, not necessarily a scratch 2. organism = Bartonella henselae III. Actinomycosis A. Etiology 1. species: A. israelii, A. naeslundi, A. viscosus, A. odontolyticus, A. meyeri, & A. bovis 2. gram (+) anaerobic bacteria
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B. Clinical features 1. sulfur granules in pus 2. wooden induration with a central soft spot 3. doesnt follow fascial planes & lymph channels 4. txmnt: long-term high dose antibiotics (6-12 wks) with PCN or TCN IV. Bullous Impetigo A. Etiology & pathogenesis 1. a superficial blistering infection of skin caused by Staph. Aureus and/or group A strep. 2. Its highly contagious and more common in children B. Clinical features 1. multiple bullae (blisters) that contain a clear fluid 2. some rupture with crusting 3. located on face, hands, elbows, & knees 4. txmnt: systemic antibiotics (PCN) IV. Mycotic Diseases A. Candidiasis (candidosis) 1. acute pseudomembranous: white plaques that do not rub off a red base thats painful 2. acute atrophic (most common type): painful, burning, erythematous mucosa 3. chronic atrophic (denture stomatitis): erythematous mucosa under a denture that may or may not be painful 4. angular cheilitis: cracking, fissuring, and pain in commissure area 5. chronic hyperplastic: white epithelial thickening on the side of the tongue that looks like hairy leukoplakia 6. median rhomboid glossitis: erythematous patch on dorsum of tongue anterior to circumvallate papillae (may or may not be painful) 7. txmnt: a. mouthrinse: Nystatin, CHX b. ointment: helpful under a denture and mouth corners (Nystatin, Ketoconazole, or Clotrimazole) c. troches (lozenges): dissolve in mouth---Clotrimazole (mycelex oral troches) d. systemic: Ketoconazole (nizoral), Fluconazole (diflucan) B. Coccidioidomycosis 1. San Joaquin Valley Fever 2. Endemic to most of the southwest 3. Etiology: dust storms allow organism to be inhaled C. Zygomycosis 1. A family of fungi (Absidia, Mucor, & Rhizopus) 2. Diabetics especially susceptible D. Aspergillosis 1. Species: A. flavus, A. niger & A. fumigatus 2. Not nearly as deadly as zygomycosis
40

E.

F.

G.

H.

3. Oral implications: allergic fungal sinusitis, post-extraction complications, & immunocompromised Cryptococcus 1. Species: Neoformans 2. Grows in soil & associated with pigeons 3. Also assoc. with immunosuppression 4. Enters through the lungs 5. Main complication: can cause meningitis b/c of spread to meninges 6. Txmnt: Amphotericin B Histoplasmosis 1. Species: H. capsulatum 2. Most common systemic fungal infection *** 3. Endemic to Mississippi-Ohio-Missouri River basin 4. Etiology: soil exposure in humid areas 5. Soil follows contamination by birds & bats---esp. chickens & starlings 6. See classic coin lesions 7. Clinically like TB 8. Oral mucosa is one of the most common sites outside the lungs--gingival predilection. 9. Txmnt: Amphotericin or the Imidazoles Blastomycosis 1. Species: B. dermatitides 2. Location similar to histoplasmosis, but only 1/10th as common. 3. Oral lesions: -granulomatous ulcers -intact epithelial white lesions -mixed pink to white lesions Toxoplasmosis 1. a protozoal organism 2. species: Toxoplasma gondii 3. cats are considered to be the definitive host

V. Viral Diseases A. Herpes viradae 1. HSV 1 a. acute herpetic gingivostomatitis: - occurs both in children & adults - acute onset of malaise, fever, & lymphadenopathy - see gingival swelling and erythema - multiple vesicles and ulcers can occur anywhere in oral cavity b. txmnt: supportive or acyclovir (zovirax) in extreme cases c. prognosis: self-limiting; resolves in 10-14 days d. can remain latent in regional ganglia e. virus reactivation associated with UV radiation, trauma, or immunosuppression 2. HSV 2: genital herpes
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3. Varicella Zoster a. primary infection: Varicella (chicken pox) -prodrome: malaise, fever, lymphadenopathy -macules, papules, vesicles, & ulcers on skin and oral mucosa. -successive crops of lesions occur on skin -skin lesions are pruritic -txmnt: supportive; avoid ASA in children b/c of Reyes syndrome: CNS & liver damage -a vaccine is available; questionable length of effectiveness b. recurrent infection: Zoster (shingles) -same latent state as HSV -predisposing factors: decreased immunocompetence -see in elderly patients -immunosuppressive drugs can cause this -see painful vesicles, ulcers, & crusts -see a unilateral distribution that follows peripheral nerve distribution -most common on trunk and trigeminal area 4. Epstein-Barr a. primary infection: mononucleosis b. secondary infection: chronic fatigue syndrome c. tumors: nasopharyngeal carcinoma, Burkitts lymphoma, or hairy leukoplakia 5. Cytomegalovirus a. prefers glandular tissues b. the adult primary lesion is much like mono B. Enteroviradae 1. Coxsackie virus (Group A) a. see vesicles and ulcers in posterior oral cavity: soft palate, uvula, & anterior tonsillar pillar b. resolves in several days c. Hand, Foot & Mouth disease: -vesicles and ulcers throughout the oral cavity -macules and vesicles on hands & feet: borders of palms & soles, ventral on digits -oral lesions resemble herpangina, but range 2-7mm and can be larger d. Herpangina: -fever, sore throat, nausea, vomiting, diarrhea, & lymphadenopathy -disease resolves in several days e. Acute lymphonodular pharyngitis -Coxsackie A10 B. Viral vesiculoulcerative diseases 1. Measles (Rubeola) a. incidence on the rise
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b. almost all school-aged children get vaccinated c. oral lesions: Koplik spots on buccal mucosa---these are red macules with white centers. They appear b/f the skin rash d. erythematous skin rash appears on face and spreads to trunk and extremities as the Koplik spots recede. VI. Chemical Injuries A. Mercury 1. oral manifestations -metallic taste -ulcerative stomatitis -salivary gland enlargement -macroglossia -gingiva become blue/gray to black B. Silver 1. Cause: silver nitrate in nose drops 2. Signs: diffuse grayish-black skin discoloration, especially sun exposed areas C. Bismuth 1. Signs: chronic exposure results in blue-gray skin discoloration as well as gingivae and conjunctivae. D. Melanosis 1. Common medication causes (3): -Quinines (can cause focal melanotic macules & erythema multiforme -Anti-neoplastic agents -Birth control pills

Pigmented and Vascular Lesions I. Generalized A. Developmental 1. Physiologic pigmentation -racial pigmentation (melanoplakia) -seen in dark-skinned individuals -gingiva is characteristically affected -normal # of melanocytes, but increased melanin production B. Endogenous cause 1. Peutz-Jeghers syndrome a. pigmented lesions present as freckles -they develop early in childhood -involve body orifice areas: mouth, anus, nose, & genital areas b. hamartomatous intestinal polyps -primarily affects mucous producing mucosa (jejunum, ileum)

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-often presents with obstruction due to intussusception (small intestines moving down on itself) -2-3% of patients show malignant degeneration c. oral manifestations -small blue-gray macular pigmented lesions -can involve the vermilion border, lips, & buccal mucosa 2. Addisons disease (chronic adrenocortical insufficiency or hypoadrenocorticism) a. etiology of Addisons: destruction of adrenal cortex b. clinical features: -fatigue, irritability, depression, weakness, hypotension, GI upset, anorexia, nausea, diarrhea, & weight loss -may see a salt craving c. hyperpigmentation of the skin -bronzing as a result of increased ACTH & MSH secretion -primarily in sun exposed areas d. oral pigmentation -diffuse patchy or macular lesions e. txmnt: replacement therapy (25mg hydrocortisone equivalent/day 3. Melasma (chloasma gravidarum or pregnancy pigmentation) a. diffuse, often irregular pigmentation b. involves midface, malar areas, and forehead c. etiology related to increased MSH secretion 4. Acanthosis nigricans a. symmetric brown velvety plaques with a predilection for the groin, back, or axillae b. sometimes see brown thickening over fingers, palms, and the upper lip c. palate and tongue lesions appear papillomatous C. Exogenous cause 1. Lead poisoning a. also known as plumbism b. usually due to chronic ingestion/exposure c. signs: fatigue, musculoskeletal pain, & headache (a constant headache that doesnt go away) d. can see neural deficits, peripheral neuritis (wrist, foot drop) e. orally: see gingival lead line and ulceration and/or excessive salivation (ptyalism) and metallic taste 2. Mercury poisoning a. may be acute or chronic b. most common cause could be industrial or laboratory exposure and accidental ingestion c. oral manifestations of chronic mercury poisoning: -blue-gray to black gingival pigmentation -ptyalism -metallic taste
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-salivary gland, gingival, & tongue enlargement -ulcerative stomatitis -can see bone destruction and teeth floating in air 3. Silver poisoning a. also known as argyria (argyrosis) b. see diffuse grayish-black discoloration of the skin primarily in the sun-exposed areas c. sclera and nail beds may show similar pigmentation d. orally: see diffuse bluish-black discoloration of the oral mucosa II. Localized A. Developmental 1. Ephelis (freckle) -macular pigmented lesions in sun-exposed areas -can occur on vermilion, not common intraorally 2. Lentigo simplex -tends to occur in areas not exposed to sunlight -so, depth of color does not change with sun exposure -lentigo senilis: solar lentigo; age spots, liver spots -present in over 90% over age 70, rare less than 40 -see on skin of face and vermilion -etiology: chronic sun exposure -typically see multiple lesions with irregular borders 3. Melanotic macule (focal melanosis) -focal increase in melanin deposition in the mucosa -this is the oral counterpart of freckles, except theres no association with sun exposure 4. Melanoacanthoma -uncommon lesion of unknown etiology -see an increase in the number of melanocytes throughout the epithelium. 5. Nevi a. melanocytic nevi -** most common human tumor b. congenital nevus -appears at birth -bathing trunk nevus c. blue nevus -proliferation of dermal melanocytes -2 types: 1. common blue nevus: on palate & hands 2. cellular blue nevus: on buttocks d. acquired melanocytic nevi -3 types: 1. junctional: flat; sharply demarcated, black macule

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2. compound: slightly elevated, smooth surface & tan 3. intradermal: loses pigment, papillary, & may/may not have hairs 6. Seborrheic keratosis -common lesion; increased with increased age -may be due to chronic sun exposure -skin of head & neck are the most common sites -do not see intraoral lesions -characteristic clinical appearance: stuck on raisin 7. Melanotic neuroectodermal tumor of infancy -tumor of neural crest origin -usually occurs b/f age 2 -characteristic clinical features: -most commonly seen in the anterior maxilla -its a rapidly growing pigmented mass -it destroys underlying bone (teeth floating in air) -see increased vanillymendellic acid (VMA) -txmnt: surgical excision 8. Malignant melanoma -these are tumors of melanocytes -rarely arises from pre-existing melanocytic nevus (chronic trauma may induce malignant change) -acute (and perhaps chronic) sun damage is a major causative factor -commonly seen in the head & neck area -risk factors: -fair complexion and light hair (blonde/blue eyed) -those who sunburn easily -a history of painful or blistering sunburns in childhood -personal history of melanoma, dysplastic nevi, or congenital nevi -a relative with a history of melanoma -the ABCD system to differentiate a melanoma from a melanocytic nevus: -A: asymmetry -B: borders---irregular, notching -C: color---varying shades of brown, black, red, white & blue -D: diameter--->6mm in diameter, size of a pencil eraser -melanoma is dependent on the thickness of the lesion (the depth of invasion) -txmnt: surgical excision -factors influencing prognosis: -location of lesion: certain sites have a worse prognosis compared to lesions of equal thickness in other locations: -BANS:
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-interscapular area of the back -posterior upper arm -posterior & lateral neck -scalp -oral lesions have a much worse prognosis! -types of melanoma: a. superficial spreading melanoma -most common form of melanoma (70%) with radial growth -see a macular to a slightly raised lesion b. acral lentiginous melanoma -most common form of melanoma in blacks -most common form of oral melanoma: seen on hard palate, gingiva, or alveolar mucosa -common locations: palms of hands & soles of feet, nail beds (subungual areas) & mucous membranes -begins as a macule and progresses to a nodule -common in older people (6th-7th decades) c. nodular melanoma -15% of cutaneous melanomas: 1/3 occur in head & neck areas -lesion begins in the vertical growth phase -clinical presentation: nodular lesion, deeply pigmented -poor overall prognosis d. lentigo maligna melanoma B. Endogenous cause 1. Albrights syndrome (McCune-Albright's syndrome) a. polyostotic fibrous dysplasia b. can see pathologic fractures with pain & deformity c. can see a leg length discrepancy (hockey stick deformity) d. precocious puberty e. caf-au-lait spots -irregular like the coast of Maine -often overlies bone affected with fibrous dysplasia -abnormalities where you see caf-au-lait spots: 1. neurofibromatosis 2. Albrights syndrome 3. Nevoid basal cell carcinoma 4. Cowdens syndrome 5. Tuberous sclerosis 6. Ataxia telangiectasia 7. Gauchers syndrome 2. Neurofibromatosis a. autosomal dominant b. see multiple neurofibromas (like a bag of worms) c. caf-au-lait pigmentations: smooth border like the coast of California d. Lisch nodules of the iris
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e. Axillary freckling (Crowes sign) 3. Encephalotrigeminal angiomatosis (see below) 4. Hereditary hemorrhagic telangiectasia (see below) C. Exogenous cause 1. Drug induced pigmentation a. drugs that can cause intraoral pigmentations: 1. BCPs 2. Antimalarial medications 3. Chemotherapeutic agents 4. antiarrhythmic agents (quinidine) 5. Minocycline 6. Tranquilizers (chlorpromazine) 7. Anti-AIDS meds 2. Hairy tongue a. accumulation of keratin on filiform papillae b. decreased keratin desquamation c. etiologic factors: SMOKING d. clinical: see on midline of dorsum of tongue; just anterior to the circumvallate papillae (lateral and anterior areas not affected) 3. Amalgam tattoo a. inclusion of amalgam fragments in the tissue b. lesions are usually macular III. Vascular Lesions A. Hemangioma -a benign proliferation of blood vessels -usually affects younger age groups (head & neck common) -hemangioma subtypes: 1. Capillary -red to purple -spontaneous involution -no bruit or thrill 2. Cavernous -purple to dark blue lesion -often involves deep structures -does not regress -no bruit or thrill 3. arteriovenous malformation -purple to dark blue lesion -bruit or thrill present B. Varicosities (varices) -abnormally dilated, often tortuous vein -increased incidence with advancing age -no assoc. with cardiopulmonary disease or HTN -can see sublingual varices (caviar tongue)
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C. Telangiectasia -dilation of small diameter blood vessels -nose & face most common location (spider angiomas) -more common in older individuals D. Kaposis sarcoma -unknown etiology -human herpes virus 8 (HHV 8) recently shown as having an etiologic role -usually affects skin of lower extremities; oral lesions are rare -oral lesions are common in immunocompromised patients or those with AIDS -has patch, plaque & nodular stages E. Encephalotrigeminal angiomatosis -developmental anomaly -persistence of a vascular plexus around the cephalic portion of the neural tube -clinical: see port wine stain of the face following distribution of the trigeminal nerve (lateral bridge of nose & upper lip are often involved) -skull radiographs reveal classic tram-track calcification -can treat with laser therapy F. Submucosal hemorrhage -petechiae, purpura, ecchymoses, or hematoma -most often blue, black in color -etiology: usually trauma (blunt trauma; blow or biting) -non-traumatic causes: thrombocytopenia purpura Syndromes of the Head & Neck Chromosomes -22 homologous pairs that are alike in females & males called autosomes -2 sex chromosomes either XX or XY -the short arm is designated p (petite); the long arm is q (the next letter) -alterations may be numerical (addition or subtraction) or structural (deletion or translocation) -alteration in sex chromosome #: -loss of an X in female: 45X or Turners syndrome (1/3000 births) -loss of an X in male: 45Y is lethal -extra X in female: 47XXX is superwoman (1/200 births) -extra X in male: 47XXY is Klinefelters syndrome (1/850 births) -alterations in autosome #: -loss of autosomal info (monosomy) generally represents too much genetic info loss to permit a live birth -a gain in autosome # (trisomy) is compatible with life, but results in severely handicapped infants with a shortened life-span (Ex: trisomy 21 or Downs syndrome---47XY (1/700 births)) -definitions: -proband: the individual who initially presents with an identifiable disorder prompting genetic study.
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-dominant: a trait expressed in the heterozygous state. -recessive: a trait that requires homozygosity to be expressed (both parents must pass this trait on and it must be homozygous). -incomplete dominance: failure of one gene to dominate. -penetrance: the %age of times when a trait is manifested by individuals carrying the gene for that trait. -expressivity: the extent or degree to which the inheritable traits are manifested by an individual. -modes of genetic transmission-inheritance 1. autosomal dominant -most common form: one parent must be affected and will transmit the gene to of their children regardless of gender -an unaffected child will never transmit the disease -usually develop clinical signs later in life 2. autosomal recessive -must be homozygous for trait to be expressed -individual inherits one mutant gene from each parent who are usually clinically normal, but are carriers -age of onset is early 3. X-linked a. Dominant -relatively rare -all daughters of an affected father will have the disorder (females more than males) -best known disorder is Vit D resistant rickets -in some disorders, the condition is lethal is males (incontinentia pigmenti, oral-facial-digital) b. Recessive -expressed in males, because the mutant X gene does not have paired alleles on the Y (male is hemizygous) -females must be homozygous to express the trait fully -males transmit to their daughters -Ex: albrights syndrome, ectodermal dysplasia, amelogenesis imperfecta 4. Y-linked -only one trait is known to be located on the Y chromosome: hairy ears (hypertrichosis of pinna)

I. Syndromes involving bone A. Polyostotic fibrous dysplasia -monostotic is more common with only single bone involvement -polyostotic has 2 types: 1. Jaffes type: relatively few bones involved; see pigmented macules
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2. Albrights syndrome: almost all bones involved; see pigmented macules, and endocrine disturbances -clinical features of albrights syndrome: 1. begins early in life 2. bone pain 3. thickening and bowing of long bones: hockey-stick deformity 4. see spontaneous fractures 5. facial asymmetry 6. caf-au-lait spots on skin over areas of affected bone: light brown melanotic macules with irregular margins like the Coast of Maine -radiographic features of albrights syndrome: 1. poorly defined radiopaque lesions: orange peel or ground glass appearance -endocrine: precocious puberty in females -oral: may see abnormal eruption of teeth -prognosis: depends on extent of bone involvement: Jaffes type has a better prognosis than Albrights B. Osteogenesis imperfecta -most common inherited bone disease ** -both autosomal dominant and recessive hereditary patterns -osteoblasts produce abnormal osteoid -clinical features of OI: 1. blue sclera 2. opalescent dentin 3. hearing loss 4. hyperthermia, resulting in excessive sweating 5. MVP that may req. antibiotic prophylaxis 6. Increased capillary bleeding due to decreased platelet aggregation. This results in epistaxis, hemoptysis, and easy bruising -2 types of OI: 1. OI congenita: severe form with multiple fractures that often result in neonatal death 2. OI tarda: less severe form and compatible with normal life -skeletal features: 1. multiple fractures and deformity of long bones 2. large skull with prominent frontal bossing 3. kyphosis: increased curvature of thoracic spine 4. scoliosis: lateral deviation in the normally straight vertical line of the spine 5. hyperextensible joints 6. brittle bones that grow abnormally 7. bones fail to remodel -dental management of OI:
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1. SBE coverage if have MVP 2. Gentle handling of patient 3. Full crowns to prevent rapid attrition and loss of VDO C. Dentinogenesis Imperfecta -clinical features: 1. OI and DI can occur independently 2. Only the dentin of the tooth is affected (primary teeth more severely affected than permanent teeth) -oral findings: 1. teeth appear translucent (blue, brown, or gray): opalescent 2. teeth have bulbous crowns with thin necks and roots (roots fracture easily) 3. pulp chambers can be enlarged or obliterated with irregular dentin of decreased hardness 4. enamel is normal, but fractures off rapidly ** D. Gardners syndrome -75% of patients have dental abnormalities that present early -its associated with malignancy (both colon and thyroid) -see polyps of the large intestines: these are not found in every patient, but a huge majority. ** If polyps are present, theres a 100% incidence of colon carcinoma -clinical features: 1. see osteomas of bones (osteoma is a benign neoplasm) 2. see multiple epidermal cysts 3. see fibrous tumors of the skin 4. ** see multiple unerupted permanent and supernumerary teeth -management: 1. patients w/out polyps should be evaluated periodically 2. do colectomy once polyp is detected -** 5 hereditary syndromes with intestinal polyposis 1. Gardners syndrome 2. Familial polyposis coli (no osteomas here---so its Gardners w/out the osteomas, but with the polyps) 3. Peutz-Jeghers syndrome: low malignant potential of the polyps 4. Turcots syndrome: colonic polyps and brain tumors 5. Cowdens syndrome: E. Cherubism -autosomal dominant -100% penetrance in males -almost 100% in mand -clinical features: 1. usually appears around age 2-4 2. see progressive non-tender, bony hard swellings of the jaws 3. always involves the mand with maxilla involvement 60-70% of the time
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4. lower sclera is revealed: heavenly gaze 5. bony swellings produce a round cherubic face -radiographic features: 1. bilateral radiolucent lesions: expansion with thinning of cortical plates; sometimes perforation of these plates 2. see multiple unerupted teeth that are displaced by the lesions 3. see premature exfoliation of primary teeth and subsequent lack of eruption of permanent teeth -management: 1. bone can heal itself; by age 30, appearance may be normal F. Craniofacial dysplasia (Crouzons syndrome) -autosomal dominant -early closing of the coronal suture: so upper part of face stops growing -clinical features: 1. frog-like face (mid-face hypoplasia and short upper lip) 2. exophthalamus 3. hypertelorism (large interpupillary distance) 4. high arched palate with hypoplastic maxilla causing malocclusion 5. parrot beak nose -Aperts syndrome: one step further than Crouzons 1. craniofacial dysostosis with syndactyly: webbing b/w adjacent fingers and toes 2. hearing loss due to stapes fixation -management: 1. craniotomy at an early age to provide space for the brain 2. orthodontics and orthognathic surgery G. Cleidocranial dysplasia -autosomal dominant -clinical features: 1. unlike craniofacial dysplasia where the sutures close early, these stay open or have late closure 2. since the sutures remain open, wormian bones are produced 3. see prominent frontal, parietal, & occipital bones 4. shoulder: aplasia, hypoplasia, or thinning of clavicles---resulting in hyper-mobility of the shoulders 5. orally: high arched palate, small max compared to mand, prolonged retention of primary teeth with resultant severe malocclusion -radiographic features: 1. multiple unerupted supernumerary teeth -management: ortho or oral surgical management of unerupted permanent teeth H. Mandibulofacial dysostosis (Treacher-Collins syndrome) -clinical features:
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1. face -downward sloping of palpebral fissures -hypoplasia of the mand (sever class II) -large fish-like mouth 2. eyes -congenital fissure (colobama) affecting lwr 1/3 of lid -deficiency of eyelashes (esp on lwr lid) 3. ears -deformed pinna -may see hearing loss 4. oral -hypoplastic mand with resultant malocclusion -high-arched palate, sometimes cleft -management: 1. surgery on eyes, ears, and jaws 2. ortho txmnt & orthognathic surgery I. Marfans syndrome -autosomal dominant -defective cross-linking of collagen (believed Abraham Lincoln had this) -clinical features: 1. increased length of tubular bones and long, thin extremities 2. arachnodactyly: spidery fingers 3. long and narrow skull (dolichocephalic) 4. hyperextensible joints 5. aortic aneurysm or MVP with regurgitation (req SBD prophylaxis)---may give B-blockers to reduce stress on aorta J. Downs syndrome (Trisomy 21, Mongolism) -95% of cases due to an extra 21st chromosome -incidence arises with increased maternal age (avg = 35) -clinical features: 1. mental retardation 2. flat face with slanted eyes an open mouth breathing 3. macroglossia, with protrusion of tongue -oral findings: 1. advanced perio 2. enlarged lingual papillae resulting in a pebbly tongue 3. high-arched palate 4. enamel hypoplasia and microdontia 5. congenital heart disease is common---SBE prophylaxis if theres a murmur -prognosis & treatment: 1. life expectancy at birth is about 16 years 2. if survive 1st year of life, longevity increases to more then 25 yrs.

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3. most common cause of death: pneumonia and congenital heart disease II. Syndromes involving skin A. Neurofibromatosis (von Recklinghausens disease of skin) -a defect in chromosome 17 -autosomal dominant -clinical appearance: 1. skin lesions: -multiple neurofibromas: well circumscribed, elevated nodules -found mainly on face, trunk, & extremities -caf-au-lait spots: may be present at birth and increase during first 3 decades---will see the macules with regular margins like the Coast of California 2. oral lesions: -oral neurofibromas in 7-20% of patients that may be well circumscribed or diffuse -may see HTN secondary to pheochromocytomas B. Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome) -aka: Jaw cyst-basal cell nevus-bifid rib syndrome -autosomal dominant -seen in BCCs same location, but BCC is solar damage, not genetic -case report of gene defects in non-syndrome associated OKCs -skin: 1. multiple BCCs on cheeks, upper eyelids, nose, & trunk 2. see palmar & plantar pits (pits on hands & feet) and hyperkeratosis of palms and soles 3. see cysts & tumors such as epidermal cysts, lipomas, & fibromas -bone: 1. multiple OKCs of the jaws with a high recurrence rate 2. bifid ribs 3. kyphoscoliosis 4. calcification of the falx cerebri -management: Mohs surgery

C. Peutz-Jeghers syndrome (Hereditary intestinal polyposis syndrome) -see small brown melanotic macules on buccal and labial mucosa, gingiva, & the hard palate -on face, see these macules around the eyes, nose, & lips -intestinal polyps: 1. primarily involve the small intestines 2. polyps cause bowel obstruction
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3. polyps are hamartomas with low malignant potential (1-2%) D. Papillon-Lefevre syndrome (Juvenile periodontosis with palmar-plantar hyperkeratosis) -autosomal recessive -very rare (1 in 1 million births) -clinical features: 1. juvenile periodontitis: advanced alveolar bone loss involving the primary and permanent dentition 2. gingivitis and formation of deep pockets occurs 3. see premature loss of teeth 4. by age 4, all primary teeth are lost, all permanent teeth are lost by age 14 -skin lesions: 1. hyperkeratosis of palms of hands and soles of feet (can suspect at birth due to increased redness) 2. the skin involvement remains throughout life E. Multiple endocrine neoplasia syndrome, type III (MEN III) -autosomal dominant -deletion on chromosome 10 -clinical features: 1. medullary carcinoma of the thyroid: carcinoma of parafollicular cells that can metastasize and cause death 2. pheochromocytoma of the adrenal medulla -oral manifestations: 1. mucosal neuromas: see large blubbery lips that appears early in life (can also involve the tongue, palate, & buccal mucosa) 2. they dont recur after excision -txmnt: 1. prophylactic removal of thyroid (monitor for elevated levels of calcitonin) 2. periodic tests for pheochromocytoma (monitor levels of VMA in urine

F. Ectodermal dysplasia -Hypohydrotic is the best known type of the 121, and its X-linked recessive with a male predominance -clinical features: 1. see partial or complete lack of sweat glands, sebaceous glands and hair follicles (results in heat intolerance and fever) 2. prominent frontal bone and supraorbital ridges
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3. midfacial hypoplasia 4. saddle nose: depressed nasal bridge 5. skin and nails: -scalp and body hair is fine and sparse -scanty eyelashes and eyebrows -oral features: 1. hypodontia or anadontia of both dentitions 2. small conical teeth 3. impacted and unerupted teeth 4. decreased # of salivary glands resulting in xerostomia -management: 1. cool environment 2. artificial tears and saliva 3. lubricant for dry skin 4. dental prostheses to restore missing teeth -syndromes with multiple unerupted teeth **: 1. Gardners syndrome 2. Cherubism 3. Cleidocranial dysplasia 4. Ectodermal dysplasia G. Cowdens syndrome (Multiple hamartoma and neoplasia syndrome) -autosomal dominant -clinical features: 1. multiple trichilemmoma of skin 2. palmar & plantar keratosis 3. adenomas of thyroid seen in 60% of cases 4. GI polyps 5. Fibroadenoma and fibrocystic disease of the breast in 75% of affected females---breast carcinoma is most common malignancy -oral features: 1. multiple nodular and papular lesions resulting in cobblestone morphology 2. most common sites for these are the tongue, buccal mucosa, & gingiva

H. Osler Weber Rendu syndrome (Hereditary hemorrhagic telangiectasia) -autosomal dominant -clinical features: 1. profuse and often recurrent epistaxis 2. multiple telangiectasia of nasal mucosa (80%), face (60%) and hand & feet (30%) 3. GI bleeding
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I.

-oral features: 1. small reddish-purple papules usually found on the lips, tongue, & buccal mucosa 2. palate and gingiva may also be involved 3. papules blanch with diascopy -differential includes CREST syndrome Ehlers Danlos syndrome -a groups of C.T. disorders -most common variants are inherited as autosomal dominant -problems attributed to abnormal production of collagen -clinical features: 1. hyper-elasticity of skin and hyper-mobility of joints 2. excessive ecchymosis following the slightest injury 3. unusual wound healing with scarring---termed papyraceous scarring that resembles crumpled paper -oral features: 1. hyper-extensibility of the tongue (Gorlins sign: ability to extent tip of tongue to tip of nose 2. frequent sub-luxation of TMJ 3. increased incidence of periodontal disease 4. may see an inability to retain sutures

III. Modes of transmission A. Autosomal dominant: 1. Osteogenesis imperfecta 2. Cherubism 3. Craniofacial dysostosis 4. Cleidocranial dysplasia 5. Marfans syndrome 6. Neurofibromatosis 7. Nevoid basal cell carcinoma syndrome 8. MEN III 9. Cowdens syndrome 10. Osler-Weber-Rendu syndromes B. Autosomal recessive: 1. Papillon-Lefevre syndrome 2. Ehlers Danlos syndrome C. X-linked dominant 1. Rickets 2. Incontinentia pigmenti D. X-linked recessive 1. Ectodermal dysplasia 2. Albrights syndrome
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3. Amelogenesis imperfecta

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