1. White lesions of the oral mucosa Differential Diagnosis of Oral and Maxillofacial lesions 1. White lesions of the oral mucosa 2. Solitary oral ulcer and fissures 3. Yellow conditions of the oral mucosa 王文岑 高雄醫學大學 牙醫學系 高醫大附設醫院S 棟 2 樓 口腔病理影像診斷科 07-3208284; wcwang@kmu.edu.tw

White lesions of the oral mucosa Keratotic Lesions 1. Leukoedema 2. Linea alba buccalis 3. Leukoplakia 4. Nicotinic stomatitis, snuff-dipper’s lesion 5. Benign migratory glossitis and mucositis 6. Lichen planus 7. Papilloma, verrucous vulgaris 8. white exophytic squamous cell carcinoma, Verrucous carcinoma 9. Hypertrophic candidiasis 10. White sponge nevus

Sloughing, pseudomembranous, necrotic lesions Plaque Traumatic ulcer Pyogenic granuloma Chemical burns ANUG Candidasis

Ulcers Short-term ulcers Traumatic ulcers (most) Recurrent aphthous ulcers (minor) Recurrent intraoral herpes simplex lesions Ulcers as result of odontogenic infection Ulcers with generalized mucositis or vesiculobullous disease Ulcers secondary to systemic disease

Persistent ulcers Traumatic ulcers (occasional) Ulcers from odontogenic infection Squamous cell carcinoma Chancre Gumma Ulcer secondary to systemic disease Low-grade mucoepidermoid tumor Metastatic tumor

Normal Color of Oral Mucosa 1). dark pink (reddish) to very pale (almost white). 2). thickness of epithelium, degree of keratinization A). thicker epithelium: more keratinized, more fibrous and less vascular subepithelial connective tissue--color is whiter; hard palate, fixed gingival, dorsal surface of the tongue. B). darker pink or more reddish in color: less keratin, more vascular tissues; vestibule, floor of the mouth, ventral surface of the tongue, retromolar regions. C). normal variations pigmentations. D). substances in the blood, i.e. hemoglobin level polycythemia (red, cherry red) anemia (pale).

Healthy oral mucosa

Healthy oral mucosa

non-malignant variation of normal mucosa. Leukoedema non-malignant variation of normal mucosa. most often at buccal mucosa, but also other sites (labial mucosa, soft palate). most often seen adults > 40 yrs. clinical features: early stage: firmly opalescence; later stage: definite grayish white cast with coarsely wrinkle surface which cannot be removed with a tongue blade, but will disappear on stretching. (if injury: red eroded area, mimic cheek biting).

Leukoedema

Leukoedema

Leukoedema microscopic findings: increased thickness of epithelium. marked intracellular edema (ballooning) acanthosis: abnormal thickening of the spinous layer (may be severe with elongation, thickening, blunting, and confluence of the rete pegs or may consist only of their elongation). parakeratosis: hyperkeratosis with retention of nuclei.

Leukoedema

leukoplakia, cheek-biting lesion, white sponge nevus. Treatment: Leukoedema D.D. leukoplakia, cheek-biting lesion, white sponge nevus. Treatment: no treatment is required

Linea alba buccalis usually on buccal mucosa near the occlusal plane. usually bilateral, may be related with occlusal trauma, therefore more prominent if patient has little overjet of molars and premolars. Microscopic findings: increased thickness of epithelium, or hyperorthokeratosis (hyperkeratosis without retention of nuclei). Treatment: no special treatment, to avoid bite injury, change the relationship of upper and lower teeth (new denture or orthodontic treatment)

Linear alba

Leukoplakia White patch keratotic change occurring on mucous membranes. usually caused by chronic irritation. important etiologic factors including: smoking, cold temperature, hot and/or spicy foods, alcohol, betel nut and /or tabacoo chewing, occlusal trauma, sharp edges of prostheses or teeth, actinic radiation.

Leukoplakia Clinical features: asymptomatic, old age group (40–70 yrs). most happened at: tongue, floor of the mouth, lower lip, commissures, palate, mucobuccal fold, alveolar ridge, retromolar area, buccal mucosa. D.D. first R/O lesions of sloughing pseudomembranous types. easy to scrap off or not? if not, lesions are keratotic and need to D.D. with many white lesions.

Homogeneous thick leukoplakia

Leukoplakia

Speckled leukoplakia

Non-homogeneous thick leukoplakia

Verrucous leukoplakia

Verrucous leukoplakia

Verrucous leukoplakia

Hairy leukoplakia Special types of Leukoplakia AIDS patient: irregular surface like hair. acanthosis with marked hyperparakeratosis with formation of ridged and keratin projections, areas of ballooning cells and little or no inflammation in the connective tissue. Ballooning changes = koilocytes: enlarged cells, some with enlarged nuclei with perinuclear halos, others are pyknotic nuclei. (papilloma-like virus) ,(EM: EB virus), (Immunofluorescence staining for EB virus capsid antigens).

毛狀白斑 (Hairy leukoplakia) EB病毒感染引起

Hairy Leukoplakia on margin of tongue in a homosexual man

Koilocytes: Hairy leukoplakia

Lesion due to corroded amalgam fillings lingually in mandibular molars, similar with hairy leukoplakia

D.D. of hairy leukoplakia in AIDS 1. lesions due to restorative materials: corroded amalgam fillings, white lesions will disappear within a few weeks after fillings are replaced by plastic material. 2. leukoplakia: a. idiopathic leukoplakia: often located on tongue (inferior surface), usually middle-aged women, extensive and smooth surface. b. tobacco-associated leukoplakia: border of tongue, well-defined, smooth surface, regress after stop smoking.

D.D. of hairy leukoplakia in AIDS 3. lichen planus: border of the tongue, rare (reticular type). 4. chronic hyperplastic candidiasis: labial commissures extending to the buccal mucosa, disappear after fungi-static treatment.

White Sponge Nevus young, usually can be seen before puberty wide spread, usually whole oral cavity has familial pattern

D.D with lichen planus Lichen planus usually involve several lesions, leukoplakia is more often a solitary lesion. may have Wickham’s striae: fine grayish white lines arranged in a lace-like pattern may have skin lesion (leukoplakia : no skin lesion)

Lichen planus

Nicotinic stomatitis or smoker’s palate Nicotinic stomatitis or smoker’s palate, smoker’s keratosis man, pipe smokers. usually whole hard palate. reddish stomatitis changed to slightly opalescent then white. usually “red/pink dots/spots” as the centers of lesion indication inflammation of minor salivary glands. usually disappear after stopping pipe smoking.

Stomatitis nicotina palati

Snuff dipper’s lesion, Tobacco chewer’s lesion parboiled appearance of the white lesion, some are thick white plaque lesion depends on where the tobacco was contact with the mucosa. usually on the mandibular vestibule (both the incisors and the molar regions). if change the habit, then most lesions will completely disappear.

Tobacco chewer’s lesion

Hairy Tongue

White hairy tongue 1.elongation of the filiform papillae: increased retention of keratin. 2.male more than female. 3.depends on foods, the color can be different. 4.treated by tongue brushing.

Black Hairy Tongue

Black hairy tongue Caused by elongated filiform papillae. Other causes: (i) antibiotics (penicillin or tetracycline) (ii) mouthwashes (sodium perborate or chlorhexidine) (iii) iron preparations (iv) smoking (iv) some foodstuffs (v) herbs

Geographic Tongue

Geographic tongue Benign migratory glossitis and mucositis (Geographic tongue) 1.psychological influences and suspected. 2.irregularly shaped red patches and white patterns like map, on the dorsal , ventral and lateral surfaces of tongue. 3.red patches: desquamated filiform papillae: enlarge and regressive:change every week then completely disappear.

Geographic tongue 4.generally asymptomatic, sometimes burning sensation, tenderness and pain. 5. treated with : a. bland diet; b. coating the lesion with triamcinolone in Orabase, if symptoms occur

Median rhomboid glossitis

Median rhomboid glossitis May be congenital ( persistence of the tuberculum impair) or may be associated with candidal infection. Smoking may predispose to the candidosis. There is: (i) absence of filiform papillae. (ii) epithelial hyperplasia and acanthosis. (iii) chronic inflammatory infiltrate in the lamina propria.

Lichen planus 1. Affecting 0.5-2.0% of the population 2. Mean age at onset: 30-50 years 3. A mild predilection for females 4. Six forms: reticular, papular, plaque, atrophic, erosive, bullous 5. Malignant transformation -- <1% 6. Etiology: emotional stress or aberrant cellular immunity

Lichen planus 7. sites: mostly at buccal mucosa (85%), others including gingiva, tongue, palate, floor of the mouth, vermillion border, (skin: small flat papules/ulceration may fuse together).

Reticular lichen planus (Wickham’s striae)

Erosive lichen planus

Plaque type lichen planus

Erosive lichen planus Desquamative gingivitis

Lichen planus

Bullous Lichen Planus If severe liquefaction, then bullae formed; in very severe case, then disseminated erosions.

D.D.1. White sponge nevus D.D.2. Geographic tongue White sponge nevus usually appears at birth (OLP : 70% after 40 yrs.) D.D.2. Geographic tongue Geographic tongue -- red center with a slightly raised white border: rapidly (in a few days) change site and shape OLP , if change, take longer time

D.D. 3. Leukoedema D.D. 4. Linea alba Leukoedema if has wrinkles, stretching test can be used to D.D. with Wickham’s striae. D.D. 4. Linea alba Patient sucking cheeks habit, then often has linea alba and mimic Wickham’s striae: asking about patient’s habit.

D.D. 5. Lichenoid reactions History of taking drugs: a. systemic treatment with streptomycin, tetracycline, hypoglycemics, diuretics, indomethacine…. b. dental restorative materials: dental gold, mercury, silver alloys.

Papules Lichen Planus

Management: OLP no treatment jf no discomfort, examined periodically. clinical discomfort ( i.e. burning , tenderness, soreness of oral mucosa): topical steroid severe cases: systemic administration of sedative and cortisone.

Squamous cell papilloma, papilloma

Squamous cell papilloma Features: 1. exophytic, papillomatous shape, pedunculated with rough, cauliflower-like pebbly surface, deep cleft formation. 2. In oral cavity, usually < 1 cm 3. site: tongue (33%), palate, buccal mucosa, gingiva, lips, mandibular ridge, mouth floor

Squamous cell papilloma 1. age: most 21-50 yrs (<40yrs) 2. Not usually in oral cavity, 3. malignant change: very rare (no dysplastic changes) 4. color (depends on whether chronic irritation)hyperkeratosis or not  white or pink.

Verrucous hyperplasia Exophytic mass (a proliferative epithelial lesion), like papilloma. Precancerous lesion Epithelial hyperplastic fold towards mucosa surface. If malignant change: towards underlying connective tissue (some scholars believe: VH =CA). Betel nut chewing habit in Taiwan

Verrucous hyperplasis

Verrucous hyperplasis

Verrucous hyperplasis

Verrucous hyperplasis

Verrucous hyperplasis

Verrucous hyperplasis *management: surgical removal. microscopic findings: confined the final diagnosis.

Verrucous carcinoma 1. an exophytic type of low-grade SCC. 2. features: 1). most sites: mandibular labial and buccal vestibule and mucosa. 2). older ages: average 60-70 yrs. 3). may be very large papillary mass or flat covered whole mucosa (sessile base). 4). color depends on the amount of keratin: pink or white. 5). may be moderately firm, but not so hard like invasive CA.

Verrucous carcinoma 3. Management: 1). wide excision:5-yr survival rates as high as 75%. 2). followed-up carefully: a tendency for multifocal tumors to develop after excision. 3). radiation: not very successful due to low grade tumor, on the contrary, radiation may induce malignancy.

Verrucous Ca.

Distinguishing histologic features between VH and V ca: s: VH, sharp varity; b: VH, blunt varity; c: V. ca

Verruca vulgaris 1. exophytic growth of the epithelium: very common lesion of the skin, rare in the oral cavity. Induced by HPV. 2. features: site: skin, vermillion border, rarely on labial or buccal mucosa or tongue.

Verruca vulgaris (common wart)

D.D. with papilloma and verrucous vulgaris verrucous vulgaris: usually on skin, rarely in the oral cavity. …sessile base vs. pedunculated (papilloma). …round eosinophilic bodies in the cells ( in prickle cell layer and granular cell layer) : viral inclusion bodies( not seen in papilloma).

Squamous cell papilloma verrucous vulgaris

Squamous cell carcinoma

Squamous cell carcinoma

Oral Candidiasis Moniliasis, candidosis Classification A. Acute pseudomembranous (Thrush) B. Acute atrophic (antibiotic sore mouth) C. Chronic atrophic (denture-associated stomatitis) D. Chronic hyperplastic (chronic mucocutaneous candidosis; candidal leukoplakia)

Chronic candidiasis if low grade infection by Candida albicans: due to long term irritation: ( i.e. tobacco smoking) increase keratin production and retention  hyperkeratosis, like leukoplakia  can not be scraped off

Chronic Mucocutaneous Candidiasis

Acute pseudomembranus type candidiasis

Acute pseudomembranus type candidiasis

erythematous cndidiasis

Factors predisposing to oral candidiasis 1. Systemic factors: physiologic old age, infancy, pregnancy 2. Endocrine disorders: diabetes mellitus, hypothyroidism 3. Nutritional deficiencies: iron, foliate, or vitamin B12 deficiency 4. Malignancies: acute leukemia, agranulocytosis, 5. Immune defects, immuosuppression, AIDS, thymic aplasia, corticosteroids

Candida Albicans

Candidiasis Management: a. discontinue broad spectrum antibiotics treatment, use more selective ones. b. anti-fungal therapy, ex. nystatin suspension c. treatment of primary diseases.

AIDS 1. Pseudomembranous cadidiasis, 2. Erythematous candidiasis: lesion on the tongue: along the mid-line and the filiform papilla atrophic. 3. If esophageal candidiasis: may be AIDS.

Oral Candidiasis as the first manifestation of HIV Infection

Submucous fibrosis 1. a fibroelastic change of the lamina propria. 2. epithelial atrophy: stiffness of the oral mucosa: trismus and inability to eat. 3. etiology: unclear, strong irritating foods and vitamin B def., protein def., betel nut chewing. Precancerous condition

Submucous fibrosis 1.Clinical: 1). burning sensation: vesicles, ulcerations or recurrent stomatitis. 2). stiffening of certain areas: difficult to opening the mouth and swallowing. 3). like systemic sclerosis or scleroderma. 4). mucosa: finally became blanched and opaque, fibrotic bands. 5). age: usually 20-40 yrs.

Submucous fibrosis

Submucous fibrosis

Submucous fibrosis

Submucous fibrosis

Submucous fibrosis 2. Microscopic findings: severe atrophic, rete pegs disappeared, epithelial atypia, disappearance of fibroblasts, blood vessels obstructed or narrowed. 3. Dense collagen bundles aggregation

Submucous fibrosis 3. Treatment: 1).could be precancerous. 2).systemic corticosteroid and local hydrocortisone to alleviate pain.

Sloughing Pseudomembranous Necrotic Lesions May be scraped off the mucosa with a tongue blade, leaving a raw bleeding surface.

Plaque Plaque (material alba): *dental plaque is on the tooth surface, not easily been washed off with water.

Chemical burns Chemical burns: 1. some analgesics put in the oral cavity: mucosal lesions: aspirin burn etc. or causatic agents (phenol, silver nitrate) used by dentist. 2. diagnosis: history. 3. treatment: protective coating: Orabase, bland diet; systemic analgesics.

chemical burn

chemical burn

chemical burn

ANUG Acute Necrotizing Ulcerative Gingivitis (ANUG, Vincent’s infection, Trench mouth) 1.inflammatory disorder of gingiva, necrotic ulcerative destruction of the free gingiva, crest and inter-dental papillae.

ANUG

ANUG 2. Predisposing factors are very important: (i). mainly due to decrease resistance to infection (ii).gingivitis and periodontitis: poor oral hygiene (iii). Stress these lead to overgrowth of the normal flora or superinfection by anaerobic and fusiform bacilli and spirochete (should be P.i.).

ANUG Differential diagnosis: 1.punched out defects of the inter-dental papillae: pathognomic for ANUG. 2.diffuse gangrenous stomatitis: necrotic gangrenous process spread to oral mucosa except interdental papillae and marginal gingiva: systemic disorders??

ANUG Management: 1.mainly aimed to : superinfection by anaerobic fusiform and spirochetes, poor oral hygiene (gingivitis and periodontitis), and low resistance to infection.

ANUG (i). antibiotics (penicillin 500mg, q.i.d. >5days). (ii). careful scaling, curettement and debridment ( best 24-48 hrs after antibiotics treatment). (iii). oral rinsing with a solution of 3% H2O2 in saline (1:3), 12x daily. (iv). recontouring of the gingiva if necessary.

Candidiasis

Angular cheilitis Predisposing factors: decreased vertical dimension of dentures, anemia, vitamin B deficiencies Infection with Candida albicans, other microorganisms Treatment: eliminate predisposing factors, antifungal ointment (nystatin)

Angular cheilitis

Angular cheilitis

Yellow Lesions Fordyce’s granules: a collection of sebaceous glands, covered by normal mucosa. clinically: small elevated granules, color from whitish yellow to yellow.

Fordyce’s granules 1. in oral cavity: buccal mucosa (usually bilateral), retromolar pad, labial mucosa. 2. usually no ulceration, looks like cheese. 3. histological features: like normal sebaceous glands of skin. 4. 50-80% population may have, a benign lesions, patient cancer phobia.

Fordyce’s granule

Fordyce’s granule

Lipoma 1. the most common benign neoplasms, but rarely in oral cavity. 2. mature fat cells under skin tissue. 3. usually after 40 yrs., peak at 50 yrs (middle age).

Lipoma 4. in oral cavity: most on buccal mucosa and mucobuccal fold, then tongue, floor of the mouth and lips. 5. usually yellow color, but many shapes: sessile, pedunculated; usually smooth surface, no-ulcerated (except with trauma). 6. palpation: nontender, soft, felling like cheese. 7. usually single lesion.

Lipoma

Lipoma 1. Microscopic findings: mature fat cells within a connective tissue capsule, fibrous stroma divided into lobules, blood vessels in the septa. 2. Treatment: excision for large lesion, no treatment for small lesions.

Epidermoid and Dermoid Cysts 1. a kinds of developmental anomalies. Cystic teratoma comes from germinal epithelium. 2. any place in the body, not usually in the oral cavity. 3. if in the oral cavity: patient may have swelling of his/her floor of the mouth. 4. at head and neck: most at floor of the mouth, then at submaxillary and submental areas.

Epidermoid and Dermoid Cysts 5. any ages, but mostly discovered in 15-35 yrs. old, nontender, various sizes, non-fixed, if no trauma: smooth surface. 6. histology classification depends on cystic contents: (i). epidermoid cyst: fluid, keratin, non- specific structures. (ii). dermoid cyst: sebaceous materials, keratin. (iii). Teratoma: many elements from different germinal layers: bone, muscle, teeth etc.

Epidermoid cysts Dermoid Cysts

Epidermoid and Dermoid Cysts Differential diagnosis: ranula, thyroglossal duct cyst, cystic hygroma, brachial cleft cyst, cellulitis, tumors, fat masses. Thyroglossal duct cyst

Oral Ulcers and Fissures Recurrent aphthous ulcer (canker sore) (RAU) and Intraoral recurrent ulcer of herpes simplex (IRHS) Both are: (i). easy recurrent painful ulcer (superficial), each time lasts 1-2 wks; (ii). usually have tender LAP (iii). spontaneous heal, no sequelae (scar formation).

RAU and IRHS Differences: (i). Etiology: RAU: psychic, allergic, microbial, traumatic, endocrine, hereditary and autoimmune mechanisms. IRHS: HSV infection, may be subclinical infection, virus became latent in nerve endings or ganglions reactivation  epithelial cells lesions.

RAU and IRHS (ii). Sites: RAU: freely movable mucosa (non-keratinized): lips, buccal mucosa, tongue, mucobuccal fold, floor of the mouth, soft palate. IRHS: fixed mucosa (keratinized): hard palate, gingiva and alveolar ridge.

RAU and IRHS 3. Management: a. in general, no treatment, heal after 1-2 weeks; b. some ones used: RAU: tetracycline mouthwash and cortisone in Orabase; analgesics (may be). IRHS: Vira-A or Zovirax cream (Acyclovir)

Minor type of Recurrent aphthous ulcer

Major recurrent aphthous ulcer

Herpetiform recurrent aphthous ulcer

Primary herpetic gingivostomatitis

Recurrent herpes labialis

Herpetiform recurrent aphthous ulcer

Tuberculosis (TB) 1. infectious organisms: Mycobacterium tuberculosis. 2. at oral cavity: uncommon, if any, rarely are primary lesion, but secondary to pulmonary lesions. 3. pulmonary lesion: sputum to small injury site of mucosa tissue, or through hematogenous spread to submucosa then proliferation to ulceration. 4. mostly at tongue then palate, lips, buccal mucosa, gingiva, frenula.

TB 5. irregular, painful ulcer, became larger slowly 6. easily to have trauma then can be mistaken as traumatic ulcer or carcinoma 7. sometimes without ulcer; if on gingival, then diffuse, hyperemic, nodular or papillary proliferation 8. sometimes involved bone (maxilla or mandible) through hematogenous spread.

Tubercurosis

Tubercles of epitheloid cells, Langhan’s giant cells, mononuclear cells in periphery

Ulcers secondary to systemic disease Differential Diagnosis of Ulcers Ulcers secondary to systemic disease 1. History of predisposing disease or history revealing information suggesting presence of disease. 2. Example: Steven-Johnson syndrome (Erythema multiform).

Erythema multiform 1. involves lips with multiple red lesions (papule or bullae): rupture: raw, painful lesions 2. other sites including skin lesions; before disease, may have HSV, taken drugs (antibiotics, contraceptives, barbiturates), post-radiation therapy ( i.e. ulcerative colitis patient).

Ulcers from odontogenic infections 1. suspicion of ulcer on alveolar or palate 2. digital pressure on alveolus or tooth elicits pus from ulcer 3. trace sinus with gutta percha cone: x-rays to isolate involved teeth.

RAU IRHS Recurrent aphthous ulcer: 1. yellowish ulcer, 0.5-2 cm diameter, with narrow erythematous halo 2. on loose mucosa surface. IRHS Intraoral recurrent herpes simplex: 1. cluster of small punctuate ulcers (< 0.5cm) 2. on bound mucosa.

Traumatic ulcers History of trauma or presence of potential etiologic agent.

Squamous cell carcinoma 1. high suspicion if patient is male over 40, heavy drinker or smoker 2. no evidence of trauma or systemic disease; negative serologic findings 3. risk factors involved: alcohol, betel quid chewing, smoking

Squamous cell carcinoma

Squamous cell carcinoma

民國九十七年台灣地區十大癌症死因 台灣地區民國97年有38913人死於癌症， 平均每13分半就有1人死於癌症 死亡率 死亡原因 每十萬人口 死亡人數 死亡率 1 肺癌 33.8 7,771 2 肝癌 33.3 7,651 3 結腸直腸癌 18.5 4,266 4 女性乳癌 13.5 1,541 5 胃癌 10.0 2,292 6 口腔癌 9.6 2,218 7 攝護腺癌 7.7 892 8 子宮頸癌 6.2 710 9 食道癌 6.2 1,433 10 胰臟癌 5.9 1,364 98.6.17公佈 台灣地區民國97年有38913人死於癌症， 平均每13分半就有1人死於癌症

民國九十七年男性與女性十大癌症死因 男性 女性 1 肝癌 1 肺癌 2 肺癌 2 肝癌 3 結腸直腸癌 3 結腸直腸癌 男性 女性 1 肝癌 1 肺癌 2 肺癌 2 肝癌 3 結腸直腸癌 3 結腸直腸癌 4 口腔癌 4 女性乳癌 5 胃癌 5 胃癌 6 食道癌 6 子宮頸癌 7 攝護腺癌 7 胰臟癌 8 胰臟癌 8 卵巢癌 9 鼻咽癌 9 白血病 10非何杰金淋巴癌 10 非何杰金淋巴癌 口腔癌男性死亡2,079人 98.6.17公佈

台灣口腔癌死亡人數統計 資料來源:行政院衛生署　製圖：王文岑