DMD714 Oral Pathology Final Exam Review PDF

DMD714 ORAL PATHOLOGY FINAL EXAM REVIEW Alivia M. Shasteen, DMD, FAAOMP, FAAOM [email protected]  MACULE Definition: Focal area of change that is not elevated or depressed in relation to its surroundings If you run your finger along the lesion, and y...

DMD714 ORAL PATHOLOGY FINAL EXAM REVIEW Alivia M. Shasteen, DMD, FAAOMP, FAAOM [email protected]  MACULE Definition: Focal area of change that is not elevated or depressed in relation to its surroundings If you run your finger along the lesion, and you feel any texture change, it is NOT a macule This is the correct term when you want to say “freckle”. Most common use: Melanotic macule May be well-defined/well-circumscribed OR ill-defined/poorly circumscribed As a GENERAL rule, lesions that have distinct, easy to trace borders are less worrisome for a malignant process than those with fuzzy, fading borders.  Definition: Papule: Solid, raised lesion that is less than 5 mm in diameter Nodule: Greater than 5 mm in diameter Can be any color but are usually pink or white if traumatized PAPULE VS. Papules and nodules are usually well- circumscribed. NODULE If they are not, the general term of “swelling” may be more appropriate. These are the correct terms for when you want to say “bump”. Papules may occur in clusters in certain disease processes Multifocal epithelial hyperplasia  PLAQUE Definition: Lesion that is slightly elevated and is flat on its surface Unlike a macule, a plaque will have some surface texture to it if you rub your finger along it. Unlike a papule/nodule, it is still mostly flat. There is no/minimal submucosal fullness. This is a term that is often associated with dysplastic lesions. Dysplastic: Potentially malignant Similar to a macule, these may be well or ill-defined and that may dictate your treatment decisions and/or differential diagnosis.  Definitions Sessile: A tumor or growth whose base is the widest part of the lesion Pedunculated: A tumor or growth whose base is narrower than the widest part of the lesion These are adjectives to describe a lesion (i.e. sessile nodule) A lesion cannot be both pedunculated and sessile SESSILE VS. PEDUNCULATED  PAPILLARY Surface projections are usually more rounded or “cauliflower-like” Often pedunculated Fibrovascular cores support the exophytic growth Exophytic: Growing outward from surrounding epithelium  VERRUCOUS Rough or warty surface “Church-spire”-like projections Pointier or spikier projections than papillomas Overlying epithelium often “cups” towards the center  Definitions: Vesicle: Superficial blister, 5 mm or less in diameter, usually filled with clear fluid Bulla: Large blister, greater than 5 mm in diameter VESICLE Can be fluid-filled but more often blood-filled Pustule: Blister filled with purulent exudate (pus) BULLA Lesions may be single or multiple depending on PUSTULE disease process or stage of healing Vesicles, in particular compared to pustules or bulla, tend to occur in clusters The fluid, blood, or purulence that is accumulating to form the swellings may be subepithelial or intraepithelial. While “blister” is not an incorrect term, using vesicle, bulla, or pustule, is more descriptive.  EROSION AND ULCERATION Definitions: Erosion: Partial or total loss of the surface epithelium Ulcer: Lesion characterized by the loss of surface epithelium (and often some of the underlying connective tissue). As a result of this loss, ulcers are often depressed or excavated. Ulcers have all had mucosal erosion, but not all lesions that show erosion are ulcers. “All squares are rectangles but not all rectangles are squares” If erosive lesions have not lost the full thickness of epithelium, they are not ulcers Example: Lesions from chemical burns (seen here) Ulcer is another term that is often misused on pathology submission reports. Just because something is irritated or inflamed does not mean it is ulcerated.  PETECHIAE VS. ECCHYMOSIS Definitions: Petechia: Round, pinpoint area of hemorrhage Ecchymosis: Non-elevated area of hemorrhage, larger than a petechia Unlike a bulla, an ecchymosis is not elevated. These are the correct terms when you want to say “bruise”.  TELANGIECTASIA Definition: Vascular lesion caused by dilation of a small, superficial blood vessel This is not a term used very often by general dentists, in my experience, but can be very helpful to the pathologist. When telangiectasias are seen overlying a swelling in the oral cavity, particularly in the salivary glands, it is often an ominous sign.  White coated tongue is a form of hairy tongue. Do not confuse “hairy tongue” for “hairy leukoplakia” Oral hairy leukoplakia is seen on the lateral aspect of the tongue and is caused by Epstein- Barr virus in immunosuppressed patients, such as HIV/AIDS Dysplasia is not noted in hairy tongue Treatment for coated/hairy tongue Gently scrape tongue with toothbrush or tongue scraper Eliminate causative agents (smoking) Manage xerostomia and encourage adequate hydration Overall oral hygiene instruction  shutter PSEUDOMEMBRANOUS CANDIDIASIS AKA “THRUSH” Candidiasis is by far the most common oral fungal infection. Causative organism: Candida albicans Albicans is Latin for “becoming white” C. albicans exists in 2 forms (dimorphic) Yeast form: Fairly innocuous Hyphae form: Form that invades the host. Microscopically, as pathologists, we must see the hyphal form of Candida in order to diagnosis the patient with candidiasis  PSEUDOMEMBRANOUS CANDIDIASIS White plaques that resemble cottage cheese or curdled milk Often initiated by broad-spectrum antibiotics or immune impairment (HIV/AIDS, leukemia) Thrush from antibiotics is usually rapid, from immunocompromised status is usually slower onset Can be wiped off with dry gauze Common in infants due to underdeveloped immune system Mild burning sensation if any sensation at all Plaques are characteristically distributed on the buccal mucosa, palate, and dorsal tongue  MORSICATIO O Chronic mucosal chewing Higher prevalence in patients who are stressed (dental students?) or who exhibit psychologic conditions.  TOOTHPASTE OR MOUTHWASH REACTION Filmy whiteness; leaves normal appearing mucosa when rubbed off (This is an example of when sloughing of epithelium does not necessarily mean the lesion is ulcerated.) Sodium Lauryl Sulfate is a surfactant that may cause a reaction Form of allergic contact stomatitis Superficial epithelial desquamation  SECONDARY SYPHILIS Mucous patch of secondary syphilis May be only partially scraped off Occurs approximately 4-6 weeks after initial infection Caused by Treponema pallidum Spirochete Buir'S JUST A LITTLE MORE SYPHILIS… o Primary – Chancre Secondary – Mucous patches and condyloma lata Tertiary/Latent – Gumma Treatment of choice for syphilis is penicillin, although it may not be completely curative in patients with neurological involvement. Both syphilis and congenital syphilis are on the rise in the US!  CONGENITAL SYPHILIS Hutchinson’s triad: o Hutchinson’s teeth Mulberry molars and Hutchinson’s incisors Ocular interstitial keratitis 8th nerve deafness now  LEUKOEDEMA Bilatyda Common oral condition of unknown cause More common in black patients (70-90% of adults and 50% of children) Background mucosal pigmentation may make the edematous changes more noticeable May be more prominent in smokers Diffuse, gray-white, milky opalescent appearing mucosa stetosa PS Surface can appear folded, resulting in wrinkles on the bilateral buccal mucosa Easily diagnosed clinically by everting and stretching the mucosa The white appearance greatly diminishes Variation of normal, no treatment required Biopsies show intracellular edema in the spinous layer “Leuko” in medical terminology means white, such as leukocyte (white blood cell) Leuko-edema: White edema  Real Life LEUKOPLAKIA Defined by the WHO (World Health Organization) as “a white plaque that cannot be characterized clinically or pathologically as any other disease” Strictly a clinical description and does not imply specific histopathologic tissue alteration You will never see a biopsy report signed out as leukoplakia Exclusion of other entities that appear as oral white plaques (lichen planus, morsicatio, frictional keratosis etc.) By far the most common oral precancer When you use the term leukoplakia, there is an implication that there is a suspicion of a pre-malignant process.  LEUKOPLAKIA CAUSES Tobacco – 80% of patients with leukoplakia are smokers Tobacco pouch keratosis may not be a true leukoplakia (discussed next) Exception: Betel quid use – Associated with true leukoplakia Common in parts of Asia Alcohol – Strong synergistic effect with tobacco Conflicting evidence as to whether alcohol alone can cause leukoplakia Sanguinaria – Former toothpaste antibacterial additive Almost 10 times more likely to develop leukoplakia Typically noted in the maxillary vestibule or maxillary alveolar mucosa Ultraviolet Radiation – Lower lip exposure (Wear and recommend lip balms with SPF!) Immunocompromised patients (like transplant patients) are especially prone  LEUKOPLAKIA CAUSES Microorganisms Treponema pallidum in late syphilis Candida Unknown whether it is causative or secondarily effects previously altered epithelium Human Papilloma Virus Found 2-4 times more often in leukoplakia than normal mucosa Trauma Previously, several variants of traumatic lesions were believed to be leukoplakia but are now established to NOT be precancerous or have such a low precancerous potential that it is essentially the same as normal mucosa Examples: frictional keratosis, nicotine stomatitis, and alveolar ridge keratosis  Architectural features Cytologic features Abnormal variation in nuclear size Irregular epithelial stratification (anisonucleosis) Abnormal variation in nuclear shape Loss of basal cell polarity (nuclear pleomorphism) Abnormal variation in cell size Drop-shaped rete ridges (anisocytosis) Abnormal variation in cell shape (cellular Increased number of mitotic figures pleomorphism) Abnormally superficial mitoses Increased nuclear/cytoplasmic ratio Premature keratinization in single cells Atypical mitotic figures (dyskeratosis) Keratin pearls within rete ridges Increased number and size of nucleoli Loss of epithelial cell cohesion Hyperchromasia  LEUKOPLAKIA Because it is a clinical term only, a biopsy is required to obtain histopathologic diagnosis and to guide appropriate management Biopsies should be taken from the most clinically “severe” areas Moderate dysplasia or worse warrants complete removal if feasible An advantage of surgical excision is optimal tissue preservation for histopathologic analysis; however, can be accomplished with electrocautery, cryosurgery, or laser ablation Sometimes these other methods can distort the appearance of cells histologically. Recurrence rates range from 10% to 35%, even after removal long-term Follow-up is extremely important!  TOBACCO POUCH KERATOSIS Includes chewing tobacco, dry snuff (may have more malignant potential), moist snuff Gingival recession, tooth staining, and caries (due to sugar content) in area of tobacco contact  TOBACCO POUCH KERATOSIS The mucosa appears thin or rippled, like the sand on a beach after an ebbing tide Induration, ulceration, and pain are not associated with this lesion The altered mucosa is usually thin, almost translucent, with an indistinct border, palpation may feel soft and velvety Distinct pouch caused by flaccidity in the area of chronic tobacco placement Histopathologically non-specific (hyperkeratosis, acanthosis) Make sure to let the pathologist know that the biopsy is taken from an area where smokeless tobacco is placed. Duration of smokeless tobacco use is also helpful Epithelial dysplasia is uncommon in smokeless tobacco keratosis, and when present is typically mild reticular asymptomatic Wickestine LICHEN PLANUS Relatively common, chronic dermatologic disease that often affects the oral cavity Lichens are composed of symbiotic algae and fungi, “planus” is Latin for “flat” A variety of medications may induce lichenoid mucositis (or lichenoid dermatitis, depending on location) which presents similar to lichen planus Most common in middle-aged adults Women affected 3:2 ratio over men 1% of the population may have cutaneous lesions, 0.1-2.2% have oral lesions Skin lesions: Purple, Pruritic, Polygonal Papules on flexor surfaces of extremities 2 forms: Reticular and Erosive Erosive will be discussed later  RETICULAR LICHEN PLANUS Wickham striae – Fine, lacelike network of white lines (reticulated) Most common form is reticular, which usually causes no symptoms and often involves the posterior buccal mucosa bilaterally. The striae should be more branched and extend beyond just the occlusal plane which helps distinguish from linea alba Other oral mucosal surfaces may also be involved concurrently: lateral and dorsal tongue, gingiva, palate, vermillion border The lesions are not static but wax and wane over time Typically produces no symptoms, and no treatment is needed Occasionally can get superimposed candidiasis I typically make patients aware of the lesions and my suspected diagnosis and encourage them to let me know if they ever do experience any symptoms.  SOLAR ELASTOSIS ACTINIC CHEILOSIS/CHEILITIS Common premalignant alteration of the lower lip vermillion from chronic UV exposure Actinic means relating to the sun or light Cheilitis/cheilosis refers to inflammation of the lip More common in middle-aged to elderly fair complexioned men (10:1 M:F) (farmer’s lip, sailor’s lip) Susceptibility in patients with certain genetic disorders: xeroderma pigmentosum, albinism, porphyria cutanea tarda Early clinical findings include atrophy (smooth, blotchy, pale areas), dryness, fissures with blurring of the margin between the vermillion and the skin As the lesion progresses, rough, scaly areas develop and may thicken to form leukoplakic lesions Chronic ulceration may develop an suggest progression to squamous cell carcinoma If your patient’s lip has this appearance, ask questions! Patients will often just say their lips are chapped, but if ulceration or red/crusty surface persists, they may need some encouragement to seek a biopsy.  ACTINIC CHEILOSIS/CHEILITIS Histologically: the surface exhibits varying degrees of dysplasia Dysplasia is typically not graded in actinic cheilitis. The underlying connective tissue invariable demonstrates a band of amorphous, acellular, basophilic change known as solar elastosis UV induced alteration of collagen and elastic fibers Both solar elastosis AND dysplasia should be seen in a diagnosis of actinic cheilitis. Solar elastosis alone is not sufficient. Patients should be encouraged to reduce sun exposure, wear a wide-brimmed hat, and use sunscreen (including lip balm with sunscreen) Vermilionectomy may be performed in severe cases without obvious malignant transformation Actinic cheilosis more than doubles an individual’s risk for developing SCC  SUBMUCOUS FIBROSIS longtermusen beetle nut Histologically characterized by juxtaepithelial and submucosal deposition of densely collagenized, hypovascularized connective tissue with variable numbers of chronic inflammatory cells Dysplasia is found in 10-15% of biopsies SCC is found in at least 6% of biopsies Patients with submucous fibrosis are 19 times more likely to develop oral cancer close clinical follow-up required Does not regress with habit cessation Unlike standard smokeless tobacco keratosis May require intralesional corticosteroids, surgical splitting or excision of the fibrous bands  NICOTINE STOMATITIS Less frequent currently due to a decrease in cigar and pipe smoking Does not appear to be pre-malignant but is rather a response to heat and not the chemicals in tobacco smoke Pipe smoking tends to generate more heat Similar changes can be seen by chronic use of extremely hot beverages Palate becomes diffusely gray or white, papules with punctate red centers (inflamed salivary glands and ductal orifice) Heavy tobacco stain may be present on the teeth  NICOTINE STOMATITIS Histologically, characterized by hyperkeratosis, acanthosis, and mild patchy, chronic inflammation of the subepithelial connective tissue Squamous metaplasia of the excretory ducts is usually seen Hyperplastic ductal epithelium may be seen near the orifice Similar to tobacco pouch keratosis, nicotine stomatitis is reversible within 1-2 weeks of cessation Any persistent white lesion present after cessation should be biopsied  ORAL HAIRY LEUKOPLAKIA The most common EBV (Epstein-Barr Virus) lesion in patients with AIDS The presence of oral hairy leukoplakia is a sign of severe immunosuppression White mucosal plaque that doesn’t wipe off Most cases occur on the lateral borders of the tongue, rarely other oral mucosa is also involved  HYPERPLASTIC CANDIDIASIS In some patients with Candida, there may be a white patch that cannot be removed by scraping This form of candidiasis is the least common Most commonly on the anterior buccal mucosa Complete resolution after antifungal therapy In my experience, it may require longer antifungal therapy than other forms  LUPUS ERYTHEMATOSUS Immunologically mediated condition, most common of the “collagen-vascular” or “connective tissue diseases” In the US, more than 1.5 million people affected Several forms: Systemic lupus erythematosus Chronic cutaneous lupus erythematosus Subacute cutaneous lupus erythematosus kidature  SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) Serious multisystem disease with a variety of cutaneous and oral manifestations Increased activity of B lymphocytes and abnormal function of the T lymphocytes Precise cause unknown, but has a possible genetic component Difficult disease to diagnose in its early stages because it often appears in a nonspecific vague fashion Women affected 8-10 times more frequently than men Average age at diagnosis is 31 Common findings: fever, weight loss, arthritis, fatigue, general malaise 40-50% of patients develop the classic butterfly rash, typically spares the nasolabial folds, sunlight often makes the rash worse Kidney failure is typically the most significant aspect of the disease Cardiac involvement is also common At autopsy 40-50% of patients display warty vegetations of the heart valves: Libman-Sacks endocarditis  SLE Oral lesions develop in 5-25% of these patients (some studies suggest as high as 40%) Sometimes oral lesions appear lichenoid, but may look nonspecific Varying degrees of ulceration, pain, erythema, and hyperkeratosis may be present. Other oral complications like xerostomia, stomatodynia (burning mouth), candidiasis, periodontal disease, and dysgeusia have been described  WHITE SPONGE NEVUS kids Yufmanig Symmetrical, thickened, white, corrugated or velvety diffuse plaques affect the buccal mucosal bilaterally Other common intraoral sites include the ventral tongue, labial mucosa, soft palate, alveolar mucosa and floor of mouth, Extent varies from patient to patient Extraoral mucosal sites can also be affected: nasal, esophageal, laryngeal, and anogenital wplaneon Usually asymptomatic  HEREDITARY BENIGN INTRAEPITHELIAL DYSKERATOSIS Rare, autosomal dominant genodermatosis primarily affecting descendants of a triracial isolate (Native American, black, and white) of people who originally lived in North Carolina Reported in other areas of the US due to migration Typically presents during childhood, affecting aug both the oral and conjunctival mucosa Similar appearance clinically and histologically to White Sponge Nevus 15 Thick, corrugated white plaques involving the buccal and labial mucosa, milder cases may pool find present like leukoedema Ocular lesions develop early in life Thick opaque, gelatinous plaque adjacent to the cornea  PACHYONYCHIA CONGENITA Keratin build up Group of rare genodermatoses that are autosomal dominant Mutations of genes that encode for specific keratins are responsible for this condition The nails, especially the toenails are dramatically affected in most patients Oral lesions are not found in all patients Dependent on which keratin is mutated The free margins on the mails are lifted up because of an accumulation of keratinaceous material in the nail bed, resulting in a pinched, tubal configuration of the nail bed. Nail loss may occur Marked hyperkeratosis of the palmar and plantar surfaces produces thick callous like lesions. Hyperhidrosis of the palms and soles is common.  PACHYONYCHIA CONGENITA Oral lesions seen are thickened white plaques that involve the lateral and dorsal tongue Can involve other mucosal regions exposed to mild trauma (palate, buccal mucosa, alveolar mucosa) Histologically shows marked hyperkeratosis and acanthosis with perinuclear clearing of the epithelial cells NOTalignant No tendency for malignant transformation Most patients have to pay continuous attention to the removal of excess keratin pre Treatment of pain during walking due to blister formation under calluses How would you differentiate between pachyonychia congenita and white sponge nevus?  DYSKERATOSIS CONGENITA Usually an X-linked recessive genodermatosis (rare) Which sex would this affect more? X-linked form is caused by a mutation of a gene that disrupts the normal maintenance of telomerase, an enzyme critical in determining normal cellular longevity Other genes have been identified for other inheritance patterns Oral lesions may undergo malignant transformation  DYSKERATOSIS CONGENITA Triad of reticulated skin pigmentation, nail dysplasia, and oral leukoplakia Usually evident within the first 10 years of life Mild to moderate intellectual disability Intraorally, the tongue and buccal mucosa develop bullae, followed by erosions and eventually leukoplakic lesions 1/3 of leukoplakic lesions in these patients become malignant in a 10-30 year period, but the rate may be higher due to shortened life-span (average life span is 32 years) 80% of patients develop aplastic anemia and bone marrow failure Histologically, oral lesions will show a range of dysplasia or frank SCC Frequent oral mucosal examinations to check for malignant transformation  ERYTHEMA MIGRANS Geographic tongue, benign migratory glossitis 1-3% of the population Etiopathogenesis is unknown, likely a hereditary component Occurs commonly with fissured tongue (1/3 of patients with fissured tongue will also have erythema migrans) Can occur in other oral mucosal areas other than the tongue (benign migratory stomatitis)  ERYTHEMA MIGRANS Multiple, well-demarcated zones of erythema due to the atrophy of the filiform papillae Atrophic areas are surrounded by slightly elevated, yellow-white, serpentine (scalloped) border Appear in one area, heal, and then develop in a different area (migratory)  ERYTHEMA MIGRANS Hyperparakeratosis, spongiosis, acanthosis, and elongation of the rete ridges Collections of neutrophils (Munro abscesses) are found within the epithelium Histologically similar to psoriasis Pathologists often use the term “psoriasiform mucositis” on biopsy reports where erythema migrans/geographic tongue is suspected scoria  ERYTHEMA MIGRANS Can be asymptomatic Patient CC is often a burning or tenderness and may be worse with certain foods. Can be so severe that it interferes with nutrition Reassure the patient that this is a benign condition and no biopsy is needed However, they should be made aware that it is a chronic condition with no definitive cure Encourage them to keep a food journal and try to isolate foods that exacerbate the symptoms and avoid those foods. Textbook recommended treatment is topical corticosteroids. I might encourage oral numbing agents first to avoid complications with steroid use.  FISSURED TONGUE (SCROTAL TONGUE) 2-5% of the population Likely hereditary A component of Melkersson-Rosenthal syndrome (orofacial granulomatosis, fissured tongue, and facial paralysis)  EROSIVE LICHEN BEEPS PLANUS When ELP involves the gingiva, a process known as desquamative gingivitis can be seen Desquamative: Erosion of the overlying squamous mucosa Other conditions that can show desquamative gingivitis: Mucous membrane pemphigoid and pemphigus vulgaris A separate type of biopsy is required to differentiate between these conditions. If the erosive component is severe, epithelial separation from the underlying connective tissue may be seen, in which case the term “bullous lichen planus” may be appropriate. Rare  LICHEN PLANUS Key histologic features: “Saw tooth” rete ridges Destruction of epithelial basal cell layer Band-like lymphocytic infiltrate Degenerating keratinocytes Called cytoid or Civatte bodies Erosive form may have subepithelial separation from lamina propria  LICHENOID LESIONS Lichenoid lesions (mucositis or dermatitis depending on area affected) appear clinically and histologically similar to lichen planus but have different etiologies. Lichenoid mucositis can be caused by a variety of different medications, contactants, food additives, and dental materials (amalgam, metal crowns, etc.) Ways to differentiate: Histologically, lichenoid mucositis will have more plasma cells in the inflammatory infiltrate, whereas LP is more lymphohistiocytic Lichen planus typically shows more than one lesion, whereas lichenoid mucositis may only affect one area. Treatment for lichenoid mucositis: Identify the etiology and eliminate it (within reason)  ERYTHROLEUKOPLAKIA Leukoplakia may become dysplastic with no change in clinical appearance; however, some lesions eventually demonstrate scattered red patches (erythroplakia) Erythro – red (erythrocyte: red blood cell) These areas represent sites where the epithelial cells are so immature or atrophic that they can no longer produce keratin Erythroleukoplakia or speckled leukoplakia frequently exhibits advanced dysplasia on biopsy Mortuning core Clinical note: Not all dysplasia or leukoplakia progress. Some mild dysplasia will stay mild dysplasia forever  CINNAMON REACTION Contact stomatitis from artificial cinnamon flavoring Cinnamon oil concentrations are up to 100 times that of the natural spice Associated with products with prolonged, frequent contact such as candy, chewing gum, toothpaste Anticalculus components of “tarter-control” toothpaste are bitter Cinnamon used to mask the taste  CINNAMON REACTION Clinical presentation dependent on method of delivery. Toothpaste = diffuse, candy/gum = more localized Pain and burning are common symptoms Gingiva is most frequent site, clinically resembles “plasma cell gingivitis” Enlargement, edema, erythema Sloughing of superficial epithelium without ulceration Exfoliative cheilitis and circumoral dermatitis may occur  ERYTHROLEUKOPLAKIA Leukoplakia may become dysplastic with no change in clinical appearance; however, some lesions eventually demonstrate scattered red patches (erythroplakia) Erythro – red (erythrocyte: red blood cell) These areas represent sites where the epithelial cells are so immature or atrophic that they can no longer produce keratin Erythroleukoplakia or speckled leukoplakia frequently exhibits advanced dysplasia on biopsy Clinical note: Not all dysplasia or leukoplakia progress. Some mild dysplasia will stay mild dysplasia forever  CINNAMON REACTION Contact stomatitis from artificial cinnamon flavoring Cinnamon oil concentrations are up to 100 times that of the natural spice Associated with products with prolonged, frequent contact such as candy, chewing gum, toothpaste Anticalculus components of “tarter-control” toothpaste are bitter Cinnamon used to mask the taste  CINNAMON REACTION Clinical presentation dependent on method of delivery. Toothpaste = diffuse, candy/gum = more localized Pain and burning are common symptoms Gingiva is most frequent site, clinically resembles “plasma cell gingivitis” Enlargement, edema, erythema Sloughing of superficial epithelium without ulceration Exfoliative cheilitis and circumoral dermatitis may occur  SCARLET FEVER Systemic infection caused by group A, beta- hemolytic streptococci Tonsilitis, pharyngitis Organisms have an erythrogenic toxin that attacks blood vessels, causing the characteristic skin rash  SCARLET FEVER Children 2-13 years, usually Enathem – “Inner rash” Tonsils, soft palate, pharynx become erythematous and edematous Tonsillar crypts may be filled with yellowish exudate During the first 2 days, the dorsal tongue has a white coating through which only the fungiform papilla can be seen – white strawberry tongue t then strain  SCARLET FEVER By the fourth or fifth day, the white coating desquamates to reveal an erythematous dorsal surface with hyperplastic fungiform papillae – Red Strawberry tongue The fever develops on the second day, peaks, and returns to normal within 6 days Exanthem – “Outer rash” “Sunburn with goose pimples” Transverse red streaks in skin folds due to capillary fragility – Pastia lines Throat culture is the standard for diagnosis Treatment – Penicillin V or amoxicillin Complications: peritonsillar or retropharyngeal abscess, otitis media, acute rheumatic fever, glomerulonephritis, arthralgia, meningitis, hepatitis Other conditions that can produce white/red strawberry tongue: Kawasaki disease and COVID19  VERRUCIFORM XANTHOMA NOT d Hyperplastic condition of the epithelium with Herrelate subepithelial xanthoma cells (lipid-laden histiocytes) Verruciform: Wartlike Xanthoma: Related to fat or lipids Primarily an oral disease, but skin and genital lesions possible Likely represents an unusual immune response to localized epithelial trauma Not associated with hyperlipidemia, unlike some dermal xanthomas Demographics: More common in middle-aged adults but can be seen in any age Slight male predilection Most lesions occur on the gingiva but any site may be involved  VERRUCIFORM XANTHOMA Well demarcated, soft, painless, sessile, slightly elevated mass, with a white, yellow-white, or red color and a papillary or roughened (verruciform) surface Can be clinically similar to a squamous papilloma, condyloma acuminatum, or early carcinoma Most smaller than 2 cm NO definitive pathogenetic role of human papillomavirus (HPV) in this lesion  VERRUCIFORM XANTHOMA Papillary, acanthotic surface covered by a thickened layer of “orange” parakeratin Clefts or crypts between the projections filled with parakeratin Most important diagnostic feature: accumulation of numerous large macrophages with foamy cytoplasm (xanthoma cells) Treatment: conservative surgical excision, recurrence rare 1332 TEESE  ERYTHEMATOUS CANDIDIASIS Inflamed, red tissue with little to no white or pseudomembranous component More common than pseudomembranous candidiasis AKA acute atrophic candidiasis or “antibiotic sore mouth” Common after broad-spectrum antibiotics Diffuse loss of filiform papillae resulting in a “bald” appearance Patients often complain of a “scalded” mouth sensation Patients with xerostomia of any cause (medications, radiation, Sjogren syndrome, etc.) are more prone to erythematous candidiasis  DENTURE STOMATITIS Often classified as a form of erythematous candidiasis AKA “chronic atrophic candidiasis” Varying degrees of erythema localized to the denture- bearing areas of maxillary removable dental prosthesis Rarely symptomatic Patient will usually admit to wearing the denture continuously Rule out improper design, allergy to the denture base, or inadequate curing of the acrylic Biopsy seldom shows hyphae penetrating the keratin layer Treatment: Antifungal therapy, reiterate proper denture hygiene, soak denture overnight in Nystatin rinse  MEDIAN RHOMBOID GLOSSITIS AKA central papillary atrophy Consistent relationship between this lesion and Candida Well-demarcated erythematous zone that affects the midline, posterior dorsal tongue Usually asymptomatic  ANEMIA Iron-deficiency Seen in up to 11% of women of childbearing age, due to chronic blood loss Seen in 2% of men (GI disease such as peptic ulcer, diverticulosis, hiatal hernia, malignancy) Pernicious anemia – Vitamin B12 deficiency Anemia results in fatigue, weakness, shortness of breath, and lightheadedness Tongue appears red and atrophic or “bald” Other features of anemia: Pale oral mucosa (severe cases) Pale palpebral conjunctiva  PLUMMER-VINSON SYNDROME Iron-deficiency anemia in conjunction with glossitis and dysphagia Burning sensation of tongue and oral mucosa Angular cheilitis is often present and may be severe Abnormal bands of tissue in the esophagus – esophageal webs, and spoon shaped nails – koilonychia High frequency of both oral and esophageal squamous cell carcinoma Patients should have periodic oral and esophageal cancer screenings  PERNICIOUS ANEMIA Occurs most frequently in older patients of Northern European heritage Poor absorption of cobalamin (vitamin B12, extrinsic factor) due to a deficiency of intrinsic factor produced by the parietal cells of the stomach due to autoimmune destruction of the parietal cells Cobalamin is necessary for normal nucleic acid synthesis The cells that are the most mitotically active are affected to a greater degree (GI tract) Oral presentations of pernicious anemia are similar to that of iron-deficiency anemia  HEMANGIOMA Rarely present at birth Rapid development that occurs at a faster pace than the infant’s overall growth over 6-12 months 90% resolve by age 9, 50% resolve by age 5 The term “hemangioma” should generally be reserved for lesions of early childhood.  PLASMA CELL GINGIVITIS A distinct pattern of gingival inflammation described in the 1960-1970s Hypersensitivity to a component of chewing gum. The current list of allergens is variable Rapid onset of sore mouth The entire free and attached gingiva demonstrate a diffuse enlargement with bright erythema and loss of stippling Anterior diffuse  PLASMA CELL GINGIVITIS Psoriasiform hyperplasia and spongiosis, intense exocytosis and neutrophilic microabscesses Dense underlying plasma cell infiltrate – polyclonal A monoclonal proliferation would be suggestive of a hematologic malignancy Can look similar histologically to plaque- related gingival hyperplasia and chronic periodontitis  SUBMUCOSAL HEMORRHAGE Non-blanching, flat or elevated zone with a color that varies from red or purple to blue or blue-black Traumatic lesions are located most frequently on the labial or buccal mucosa (the areas most likely to be traumatized) Hemorrhage associated with increased intrathoracic pressure can occur on the face, neck, soft palate No treatment is usually required if the hemorrhage is not associated with significant morbidity or related to systemic disease  UPPER RE SPIRATO RY INFE CTIO NS AND S UBMUCOS AL HEMOR R H AGE Infectious mononucleosis – symptomatic disease resulting from exposure to Epstein-Barr virus Once exposed, EBV remains in the host for life In developing countries, exposure usually occurs by age 3, and is universal by adolescence In the US, exposure to the virus is delayed, 50% of college age students lack previous exposure Young adults are at greatest risk for symptomatic disease Most EBV infections in children are asymptomatic EBV is associated with oral hairy leukoplakia, various lymphoproliferative disorders and lymphomas (Burkitt lymphoma), nasopharyngeal carcinoma, salivary lymphoepithelial carcinoma, some gastric carcinomas, and more  INFECTIOUS MONONUCLEOSIS Symptoms depend on age of patient Complications are uncommon from initial infection but most frequently arise in symptomatic children Significant complications: splenic rupture, thrombocytopenia, autoimmune hemolytic anemia, aplastic anemia, neurological problems, myocarditis  ORAL LESIONS OF INFECTIOUS MONONUCLEOSIS Petechiae on the hard or soft palate NUG (necrotizing ulcerative gingivitis) Diagnosis: Peripheral blood smear >10% atypical lymphocytes on peripheral blood smear and positive heterophile antibodies. The main clinical symptoms appear to be secondary to the immune response to EBV- infected B lymphocytes  bloody lesions 164g T H RO M B O C Y TO P E N I A Markedly decreased number of circulating platelets, which are necessary for hemostasis and clot formation. The condition is often initially detected because of the presence of oral lesions. Reduced production – May be the result of various causes, such as infiltration of the bone marrow by malignant cells or toxic effects of chemotherapy Increased destruction – May be caused by an immune reaction, often precipitated by one of more that 100 different drugs Sequestration in the spleen – 1/3 of platelets are sequestered in the spleen conditions that cause splenomegaly (portal hypertension, tumor infiltration)  THROMBOCYTOPENIA Clinical evidence is not usually seen until the platelets drop below 100,000/cubic mm Severity is related to extent of platelet reduction Minor traumatic events are continuously inflicted on the oral mucosa during chewing and swallowing Clinical signs are caused by leakage of blood from damaged small capillaries without proper thrombi production Petechiae, ecchymosis, and hematoma formation Similar hemorrhagic events occur throughout the body. In severe cases ( Asian > white > black CL +/- CP is more common in males than females The more severe the defect, the greater the male predilection CPO is more common in females 80% of cases of CL are unilateral 70% of unilateral clefts occur on the left side There is ranging severity for cleft lip and cleft palate For lip, can range from a small notch to extending up to the nose For palate, can range from cleft or bifid uvula to communication with nasal cavity Management of clefting: Reduce severity during neonatal period Multiple surgical procedural repairs  PIERRE-ROBIN SEQUENCE Triad of symptoms: CP Mandibular micrognathia Glossoptosis Posterior displacement of tongue resulting in airway obstruction  Small mucosal invaginations that occur at the corners of the mouth on the vermilion border COMMISSURAL LIP PITS Male predilection Usually discovered incidentally Blind fistulae that extend 1-4 mm Fluid may be expressed representing saliva from minor salivary glands Not associated with CL or CP Does appear to be higher prevalence of preauricular pits in these patients  PARAMEDIAN LIP PITS Rare congenital invaginations of the lower lip Believed to arise from persistent lateral sulci on the embryonic mandibular arch Typically appear as bilateral and symmetrical fistulae on either side of the midline of the vermilion of the lower lip Can range from subtle depressions to prominent humps May express salivary secretions Greatest significance is that they are usually inherited as an autosomal dominant trait along with CL +/- CP This combination is called van der Woude syndrome Most common form of syndromic clefting  DOUBLE LIP Rare anomaly characterized by redundant fold of tissue on the mucosal side of the lip Upper lip is affected more often than lower Triad of Ascher syndrome Double lip Blepharochalasis (swelling of the eyelids) Nontoxic thyroid enlargement  MICROGLOSSIA Abnormally small tongue Most reported cases are associated with a group of overlapping conditions known as oromandibular-limb hypogenesis These syndromes features limb anomalies such as hypodactylia (absence of digits) and hypomelia (hypoplasia of all or part of a limb) Microglossia is associated with hypoplasia of the mandible  MACROGLOSSIA Enlargement of the tongue Pressure of the tongue against the mandible and teeth can produce a crenated lateral border of the tongue Associated with many systemic conditions and syndromes The following syndromes are associated with macroglossia with a diffuse, smooth appearance: Hypothyroidism Beckwith-Wiedemann Neuromuscular disorders The following syndromes are associated with macroglossia with a multinodular appearance: Amyloidosis NF1 MEN2B  BECKWITH-WIEDEMANN SYNDROME Rare hereditary condition that includes many other defects besides macroglossia including: Omphalocele Protrusion of part of the intestine through a defect in the abdominal wall at the umbilicus Visceromegaly Gigantism Neonatal hypoglycemia Increased risk for several childhood visceral tumors including Wilms tumor, adrenal carcinoma, hepatoblastoma, rhabdomyosarcoma, and neuroblastoma Facial features: Nevus flammeus of the forehead and eyelids Linear indentation of the earlobe Maxillary hypoplasia  LINGUAL THYROID During 3-4th week of fetal life, thyroid glands begin as an epithelial proliferation in the floor of the pharyngeal gut By 7th embryonic week, it normally descends into the neck to its final resting position anterior to the trachea and larynx The site where this descending bud invaginates later becomes the foramen cecum If the primitive gland does not descend normally, ectopic thyroid tissue may be found in this region Where 90% of ectopic thyroids are found Symptomatic lesions are more common in women In 70% of cases, this ectopic gland is the patient’s only thyroid tissue  CALIBER-PERSISTENT ARTERY Common vascular anomaly in which a main arterial branch extends up into the superficial submucosal tissues without a reduction in diameter Seen more frequently in older adults Possibly due to loss in tone in surrounding connective tissue Almost exclusively occurs on the labial mucosa, especially the upper lip The unique feature is pulsation, not only vertically but also in a lateral direction Difficult to palpate with gloves on Usually asymptomatic If clinical findings point to CPA and patient is unbothered by the lesion, no biopsy is necessary  EAGLE SYNDROME The styloid process is a slender bony projection that originates from the inferior aspect of the temporal bone Connected to the lesser cornu of the hyoid bone by the stylohyoid ligament The external and internal carotids lie on either side of the ligament The stylohyoid ligament may become mineralized (either by surgery or with aging) Usually asymptomatic but may impinge the adjacent nerves and vessels Patient experiences vague facial pain, especially while swallowing, turning the head, or opening the mouth  EAGLE SYNDROME Elongation of the styloid process or mineralization of the stylohyoid ligament complex can be seen on panoramic Classic Eagle syndrome occurs after a tonsillectomy Development of scar tissue in the area of a mineralized stylohyoid complex results in cervicopharyngeal pain in region of cranial nerves V, VII, IX and X When unrelated to tonsillectomy, may be referred to as stylocarotid syndrome Treatment depends on symptoms. Corticosteroids or surgical treatment may be required in symptomatic cases  STAFNE DEFECT Asymptomatic radiolucent lesion near angle of the mandible Classically below mandibular canal in posterior mandible Well-circumscribed May interrupt continuity of inferior border Focal concavity of the cortical bone on the lingual surface of the mandible Histologically, can contain salivary gland tissue suggesting developmental defect containing portion of submandibular gland May also be empty cavities with scant muscle, fibrous connective tissue, fat, or lymphoid tissue 80-90% of cases are seen in males Can usually be diagnosed on clinical basis by the typical radiographic presentation and lack of symptoms Biopsy is usually not necessary  NASOLABIAL CYST Rare developmental cyst that occurs in the upper lip lateral to the midline Usually appears as a swelling of the upper lip lateral to the midline resulting in elevation of ala of the nose Often elevates the mucosa of the nasal vestibule and obliterates the maxillary mucolabial fold Most commonly seen in adults with a significant female predilection Arises in soft tissue so no bony radiographic changes are seen in most cases Lined by pseudostratified columnar epithelium with goblet cells and cilia Respiratory-type epithelium Treatment recommended: complete surgical excision  NASOPALATINE DUCT CYST Most common nonodontogenic cyst of the oral cavity Believed to arise from the remnants of the nasopalatine duct Embryologic structure connecting the oral and nasal cavities in the area of the incisive canal May develop at almost any age but most common in 4th-6th decades Despite being “developmental”, rarely seen in children Male predilection Mots common presenting symptoms include swelling of the anterior palate, drainage, and pain Many lesions are asymptomatic and discovered on routine radiographs Well-circumscribed radiolucency in or near the midline of the anterior maxilla Most often round or oval with a sclerotic border Some cysts have “inverted pear” or heart shape  NASOPALATINE DUCT CYST Range in size 6 mm is usually the upper limit in size for what is considered normal for the incisive foramen In rare instances, a nasopalatine duct cyst may develop in the soft tissues without bony involvement These are called cysts of the incisive papilla Epithelial lining of NDC is highly variable, from stratified squamous to respiratory type epithelium Because the nasopalatine duct cyst arises within the incisive canal, moderate- sized nerves and vessels are often found in the wall Neurovascular bundles Treated by surgical enucleation  EPIDERMOID CYST A follicular cyst of the skin Epidermoid cyst is derived from the follicular infundibulum Follicular infundibulum is the upper part of a hair follicle Histologically similar is the epidermal inclusion cyst Occurs after traumatic implantation of epithelium Epidermoid cyst account for 80% of follicular cysts of the skin Most common in acne prone areas like head, neck, and back Unusual before puberty unless associated with Gardner syndrome Young adults are more likely to have cysts on the face while adults are more likely to have them on the back Nodular, fluctuant subcutaneous lesions Milia are tiny keratin-filled cysts that resemble miniature epidermoid cysts  EPIDERMOID CYST Microscopic examination reveals a cavity that is lined by stratified squamous epithelium resembling epidermis Well-developed granular layer is seen Lumen is filled with degenerating orthokeratin Treatment: conservative excision Topical retinoids can help with milia  DERMOID CYST Uncommon developmental cystic malformation Lined by epidermis-like epithelium but with adnexal structures in the wall Most often occur in the midline of the floor of mouth If the cyst develops above the geniohyoid muscle, sublingual swelling may displace the tongue toward the roof of the mouth Creates difficulty in eating and speaking If below the geniohyoid, can create a “double chin” appearance Most common in children and young adults Lined by orthokeratinized stratified squamous epithelium with a prominent granular cell layer Contains one or more skin appendages such as sebaceous glands, hair follicles, or sweat glands Treated by surgical removal  THYROGLOSSAL DUCT CYST Thyroglossal duct epithelium should undergo atrophy after embryogenesis Autopsy studies have shown that 7% of people will have thyroglossal tract remnants These remnants are usually asymptomatic but can give rise to cysts Classically develops in the midline and may occur anywhere from foramen cecum area of the tongue to the suprasternal notch Most are inferior to the hyoid bone Can develop at any age but most often in children and young adults Usually lined by respiratory or stratified squamous epithelium Best treated by Sistrunk procedure Cyst is removed in addition the midline segment of the hyoid bone  BRANCHIAL CLEFT CYST Developmental cyst derived from remnants of the branchial arches About 95% of these anomalies arise from the 2nd branchial arch From 2nd branchial arch, cysts occur in upper lateral neck anterior or deep to sternocleidomastoid muscle Most frequently develop in children and young adults May become evident after URI or trauma Most are lined by stratified squamous epithelium Treatment: surgical removal  PROGRESSIVE HEMIFACIAL ATROPHY (PARRY-ROMBERG) Atrophic changes affecting one side of face Uncommon and poorly understood condition Many features are similar to scleroderma (systemic sclerosis) Onset is usually during first 2 decades of life Begins as atrophy of the skin and subcutaneous structures Hypoplasia of bone may occur Overlying skin often exhibits dark pigmentation Some patients have sharp line of demarcation between affected and unaffected sides En coup de sabre (strike of the sword) Enophthalmos is common because of loss of periorbital fat Local alopecia may occur Atrophy of upper lip and tongue may occur Unilateral posterior open bite develops as a result of mandibular hypoplasia CROUZON SYNDROME (CRANIOFACIAL DYSOSTOSIS) One of a rare group of syndromes characterized by premature closing of the cranial sutures Caused by mutations on fibroblast growth factor receptor 2 gene (FGFR2) Autosomal dominant Premature sutural closing leads to cranial malformations Four variants: Brachycephaly (short head) Scaphocephaly (boat-shaped head) Trigonocephaly (triangle-shaped head) Kleeblattschadel deformity (cloverleaf skull)  CROUZON SYNDROME Orbits are shallow resulting in ocular proptosis Skull radiographs typically show increased digital markings “beaten-metal pattern” Maxilla is underdeveloped leading to midface hypoplasia Lateral palatal swellings may produce a pseudocleft  APERT SYNDROME Also associated with mutation of FGFR2 gene Typically skull pattern is acrobrachycephaly or “tower skull” Also has “beaten metal” skull pattern Ocular proptosis is common Increased intracranial pressure and exposure of eyes can result in vision loss Middle third of face is typically retruded resulting in mandibular prognathism To compensate, most infants become mouth breathers Characteristic limb defects: syndactyly Intellectual disability is common Trapezoid-shaped appearance to lips when they are relaxed as a result of midface hypoplasia and mouth breathing V-Shaped arch and pseudocleft seen Both in Crouzon and Apert, some degree of hypodontia is common  MANDIBULOFACIAL DYSOSTOSIS (TREACHER-COLLINS) Rare syndrome characterized primarily by defects of structures derived from 1st and 2nd branchial arches Autosomal dominant usually Mutations in TCOF1 gene Characteristic facies Hypoplastic zygomas Depressed cheeks Downward slanting palpebral fissures Coloboma Notch on outer portion of lower eyelid May have ear defects resulting in hearing loss Markedly retruded chin Condylar hypoplasia Lateral facial clefts  EPITHELIAL LESIONS ASSOCIATED WITH HUMAN PAPILLOMAVIRUS HPV is associated with a variety of benign, potentially malignant, and malignant epithelial lesions, but most infected individuals are asymptomatic and lack clinically evident disease. HPV types are categorized as either low-risk (6&11) or high-risk (16&18) based on oncogenic potential HPV infection is present in approximately 5%–8% of normal, healthy individuals worldwide It appears that in most people the infection clears quickly, whereas in some individuals the infection persists.  HPV + OROPHARYNGEAL CANCER Oropharynx includes soft palate, tonsils, base of tongue, and pharyngeal wall Oropharyngeal HPV+ SCC is predominantly spread through orogenital sex In countries where this practice is more taboo, this malignancy is seen less According to the CDC, HPV causes 60-70% of oropharyngeal cancer in the US Most common strain of HPV in oropharyngeal cancer: HPV16 Compared to traditional SCC, these patients tend to: Be younger Have higher socioeconomic status and education level Have no or less of a history of heavy smoking and drinking Common presenting symptom in HPV+ oropharyngeal SCC: Asymptomatic swollen cervical lymph node  SQUAMOUS PAPILLOMA Benign, papillary proliferations Can involve the oral cavity, oropharynx, and larynx Comprise 3% of all oral lesions submitted for biopsy Generally is considered to be induced by HPV, with HPV types 6 and 11 identified most commonly Sites of predilection include the palate, tongue, and lips, but any oral surface may be affected A soft, painless, usually pedunculated, exophytic nodule with numerous fingerlike surface projections that impart a “cauliflower” or wartlike appearance May be white, slightly red, or normal in color, depending on the amount of surface keratinization Conservative surgical excision, including the base of the lesion, is adequate treatment for the oral squamous papilloma, and recurrence is unlikely. Frequently, lesions have been left untreated for years with no reported malignant transformation, continuous enlargement, or dissemination to other parts of the oral cavity or oropharynx.  INFLAMMATORY PAPILLARY HYPERPLASIA Reactive tissue growth that usually, but not always, develops under a denture Some classify this lesion as part of denture stomatitis Can occur on the palate of patients who habitually breathe through their mouth and/or have a high palatal vault Candida organisms are often present but have not been definitively proven as a cause Usually asymptomatic Treatment: Improve denture hygiene, antifungal therapy In advanced cases, lesions may not heal and may require surgical excision  PROLIFERATIVE VERRUCOUS LEUKOPLAKIA A special high-risk form of leukoplakia Multiple, spreading, keratotic plaques with rough surface projections Gingiva frequently involved but can include other sites Persistent growth, usually after multiple biopsies and excisions Often develop squamous cell carcinoma within 8 years of initial PVL diagnosis Unusual in that there is a strong female predilection and minimal association with tobacco This is a clinical diagnosis, not a histologic one. The pathologist may suggest PVL if the patient has had multiple biopsies, but they may not have this information Treatment: These patients need regular monitoring indefinitely. Inform patient that they will likely need biopsies frequently. New leukoplakias should be biopsied and existing leukoplakia should be monitored for any changes in size, shape, or surface texture, which may indicate need for new biopsy.  SQUAMOUS CELL CARCINOMA Malignancy of overlying squamous epithelium Most common type of oral cancer Most common site for SCC: Lateral border of the tongue While some SCC have an ulcerated appearance, some are more exophytic ad have a papillary or verruciform surface May also have papillary surface that is also ulcerated Exophytic growths usually feel hard (indurated) on palpation Histologically, by definition, SCC must show invasive tumor islands that have budded away from overlying epithelium If there is full thickness dysplastic change but no invasive tumor, the lesion is referred to as Carcinoma In Situ In situ means “in the original place”  VERRUCOUS CARCINOMA Verrucous Carcinoma is not just SCC with a verrucous appearance! VC is a low-grade variant of SCC Some connection with smokeless tobacco use although smokeless tobacco users are still more likely to get conventional SCC Mandibular vestibule, buccal mucosa, gingiva, tongue, and hard palate Involved area may correspond to smokeless tobacco placement Diffuse, painless, thick plaque with verruciform surface Typically white Metastases are very uncommon but tumors can cause local damage Unlike conventional SCC, VC does not show invasion Diagnosis of VC is based more in the architecture of the epithelium than cytologic dysplasia  SPONGIOTIC GINGIVAL HYPERPLASIA Previously known as “Localized spongiotic juvenile gingival hyperplasia” however, it become obvious that it could be multifocal and occur in adults Idiopathic Isolated patch of junctional or sulcular epithelium that becomes exteriorized Unlike some gingival neoplasms, this does not seem to improve with better oral hygiene and plaque reduction Small, bright red, velvety or papillary patch on gingiva that bleeds easily Strong predilection for the maxillary anterior facial gingiva Although the lesion may be papillary, there is no association with HPV Treatment: Conservative excision Lesion may resolve on its own  VERRUCA VULGARIS (COMMON WART) A focal, benign, HPV-induced hyperplasia of stratified squamous epithelium, most often HPV 2. Is contagious and can spread to other parts of a person’s skin or mucosa by autoinoculation. It infrequently develops on oral mucosa but is extremely common on the skin. A painless papule or nodule with papillary projections or a rough, pebbly surface Verrucae often resolve spontaneously over time in immunocompetent individuals. Approximately two-thirds will disappear without treatment within 2 years, especially in children. However, removal may be considered for lesions that persist, spread, cause cosmetic concern, or produce discomfort. Oral lesions usually are excised surgically, or they may be destroyed by laser, cryotherapy, or electrosurgery.  CONDYLOMA ACUMINATUM (VENEREAL WART) An HPV-induced proliferation of stratified squamous epithelium of the anogenital region, mouth, and larynx. Approximately 90% of cases are attributed to HPV 6 and 11 Represents a common sexually transmitted disease (STD), affecting about 1% of the sexually active population. However, since the introduction of HPV vaccination, significant reductions in incidence have been reported in many regions Condyloma may be an indicator of sexual abuse when diagnosed in young children Oral lesions most frequently occur on the labial mucosa and lingual frenum; the soft palate often is involved as well. The typical condyloma appears as a sessile, pink, well-demarcated, nontender, exophytic mass with short, blunted surface projections Typically larger than squamous papillomas (~1.0 cm) Oral condylomata usually are treated by conservative surgical excision. Cryotherapy and laser ablation also may be used. However, there is some concern regarding the potential for laser therapy to produce an infectious plume that exposes the surgical team and patient to airborne HPV  MULTIFOCAL EPITHELIAL HYPERPLASIA (HECK DISEASE) A squamous epithelial proliferation primarily attributed to HPV 13 and 32 The condition initially was described in Native Americans and Inuits but subsequently has been noted in many populations and ethnic groups. Multifocal epithelial hyperplasia often affects multiple members of a given family; May be related to either genetic susceptibility or HPV transmission between family members Lower socioeconomic status, crowded living conditions, poor hygiene, malnutrition, and HIV infection or other immunodeficiency states appear to be additional risk factors. Multifocal epithelial hyperplasia predominantly arises in young individuals More common on buccal and labial mucosa but can be seen anywhere Treatment: Conservative excision Lesions may spontaneously recur No malignant potential  SEBORRHEIC KERATOSIS An extremely common skin lesion of older people and represents an acquired, benign proliferation of epidermal basal cells This lesion frequently affects the facial skin but does not occur in the mouth. The cause is unknown Seborrheic keratoses begin to develop on the skin of the face, neck, trunk, and extremities during the fourth decade of life They become more prevalent with each passing decade. Dermatosis papulosa nigra is a form of seborrheic keratosis that occurs in approximately 30%–77% of black patients. This condition typically appears as multiple small (1–4 mm), dark- brown to black papules scattered about the zygomatic and periorbital region Except to address aesthetic concerns or secondary irritation, seborrheic keratoses seldom are removed  DARIER DISEASE Uncommon autosomal dominant genodermatosis with striking skin but subtle oral involvement Numerous erythematous, pruritic papules on the skin of the trunk and scalp that develop during the first or second decade of life. Lesions have a rough texture and may have a foul odor due to bacterial degradation of keratin Palmar and plantar pits and keratoses Nails show longitudinal lines, ridges, or painful splits Oral lesions consist of multiple papules that may coalesce and form a cobblestone appearance. These lesions affect the hard palate and alveolar mucosa  ACANTHOSIS NIGRICANS Acanthosis: Thickening of squamous cells, Nigricans: Darkly colored Acquired dermatologic condition characterized by velvety brownish alteration of skin Can develop in conjunction with a malignancy, usually GI Malignant acanthosis nigricans The skin presentation itself is benign but may serve as an alert for internal malignancy Benign acanthosis nigricans can develop secondary to a variety of conditions, syndromes, and drugs Endocrinopathies such as diabetes, Addison, hypothyroidism, acromegaly Crouzan syndrome Oral contraceptives or corticosteroids  MALIGNANT ACANTHOSIS NIGRICANS Oral lesions are more common in the malignant form than the benign form. Diffuse, finely papillary areas that most often involve the tongue or lips, particularly the upper lip Brownish pigmentation associated with cutaneous lesions is usually NOT seen in oral lesions  TRAUMATIC ULCER & TUGSE Typically, traumatic ulcers have a yellow pseudomembrane and are surrounded by an erythematous halo Commonly occur on the lips, tongue, and buccal mucosa from biting, on the hard palate from sharp foods, and on the gingiva and vestibular mucosa from dentures Note from the pathologist: We cannot determine histologically if an ulcer is traumatic. The diagnosis will be “non-specific ulcer” or “ulcer, NOS” Except in the case of a TUGSE (traumatic ulcerative granuloma with stromal eosinophilia) Deep ulcers with a specific inflammatory infiltrate that are usually slow to resolve Rich in eosinophils Tongue is most common location Interestingly, sometimes incisional biopsy is curative and full excision of lesion is not necessary.  APHTHOUS STOMATITIS AKA Canker sores Caused by a variety of agents in different populations Three areas of causative changes Primary immunodysregulation Decrease of mucosal barrier Increase antigenic exposure Associated with systemic disorders Celiac disease, Bechet’s syndrome, Cyclic neutropenia, Ig A deficiency. Nutritional deficiencies, IBS, HIV More frequent in children and young adults 3 Clinical variations – Minor, Major and Herpetiform Treatment required: Often none Topical anesthetic such as benzocaine or viscous lidocaine may help with symptoms Topical steroids may be indicated in severe cases  MINOR VS. MAJOR APHTHOUS ULCER Minor apthae Fewest recurrences and shortest duration of symptoms Most common type Almost exclusively on the nonkeratinized mucosa Usually between 3-10 mm Heal without scarring Major apthae Ulcers are deeper and larger (1-3 cm) Also usually on the nonkeratinized mucosa May take up to 6 weeks to heal May heal with scarring  HERPETIFORM APHTHOUS ULCERS Least common of the 3 types of apthous ulcers Demonstrates the greatest number of lesions As many as 100 per occurrence Of the 3 variants, has the most frequent recurrences Tend to be closely spaced Individual lesions are small averaging from 1-3 mm Can be confused with HSV (Herpes Simplex Virus) infection “Herpeti-form” It is common for lesions to coalesce into one irregular ulceration Heals within 7-10 days Female predilection, commonly in adulthood Most common location is on the non keratinizing mucosa but can occur anywhere on the oral mucosa Diagnosis is usually made on the clinical presentation Carefully review the patient’s medical history for signs and symptoms of any systemic diseases associated with aphthous-like ulcerations Treatment: mild – no treatment or the use of topical anesthetics Diffuse minor or herpetiform: topical steriods (Dexamethasone 0.01% rinse) Major is usually more resistant to therapy and more potent corticosteroids are needed  HERPES VIRUS TYPES HHV # Virus Name HHV1 Herpes Simplex Virus 1 HHV2 Herpes Simplex Virus 2 HHV3 Varicella zoster virus HHV4 Epstein Barr virus HHV5 Cytomegalovirus HHV8 Kaposi sarcoma  PRIMARY HERPETIC GINGIVOSTOMATITIS  Typically occurs at a young age  NOT limited to keratinized mucosa  Incubation period is 2-3 days  Primary infection in adults results in pharyngotonsillitis  Small painful vesicles and ulcerations  Erythematous gingiva, skin, tongue, buccal mucosa, palate, pharynx and tonsils.  Also: fever, chills, lymphadenopathy  M (2:1)  64% have gingival involvement presenting as desquamative gingivitis  Ocular lesions occur in up to 37% of patients with MMP  Symblepharon: Surface of the conjunctiva becomes eroded. Attempts at healing result in scarring between the bulbar (near the globe) and palpebral (inner surface of the eyelid) conjunctivae  Tx: corticosteroids, Dapsone, surgery for eye lesions MUCOUS MEMBRANE PEMPHIGOID  MUCOUS MEMBRANE PEMPHIGOID Oral lesions of MMP usually begin as either vesicles or bullae Distinguishes from ELP and PV You may or may not observe this when you evaluate the patient because all vesicles may have popped.You want to be mindful if patients mention the word blisters when you see desquamative gingivitis. Vaginal lesions may cause significant pain during intercourse (dyspareunia) Somewhat specific to MMP When taking a biopsy for MMP (ideally submitted in formalin and in Michel solution for DIF), you want to submit PERI-lesional tissue, NOT the ulceration itself. It often takes multiple biopsies to solidify a diagnosis of MMP because the epithelium sloughs off during the biopsy surgical procedure. This is another reason why a DIF study is so important.  PEMPHIGUS VULGARIS  Autoimmune mucocutaneous disease characterized by intraepithelial blistering  Caused by circulating autoantibodies to desmoglein 1 and 3  Adhesion molecules  Autoantibody binding inhibits cell-cell adhesion, resulting in acantholysis and blister formation  Most common in 4-6th decades, equal sex distribution  Higher incidence in Ashkenazi Jews and patients of Mediterranean descent  Affects mucous membranes and cutaneous sites (trunk, head and neck)  “Chicken wire” pattern on immunofluorescence PEMPHIGUS VULGARIS  PEMPHIGUS VULGARIS  Mucosal PV may be only manifestation of disease or may precede cutaneous PV by ~5 months  Oral manifestations are the “first to show and last to go”  Oral mucosal lesions are presenting sign in about 5—70% of patients and 90% will have oral lesions  +Nikolsky and Asboe-Hansen signs  Nikolsky sign: Bulla can be induced if firm lateral pressure is exerted on skin  Also seen in SJS/TEN  Asboe-Hansen sign: An existing bulla can be pushed or spread if lateral pressure is applied  Treatment: local or systemic corticosteroids, immunosuppressants (methotrexate)  Mortality in up to 6% of patients usually due to systemic infection as a complication of long-term immunosuppressants  Paraneoplastic pemphigus: Rare vesiculobullous disorder in patients with a malignant neoplasm, often leukemia or lymphoma  In 1/3 of cases, paraneoplastic pemphigus was identified prior to the discovery of the malignancy TZANCK CELLS MAY BE IDENTIFIED IN PV  “TRADITIONAL” SQUAMOUS CELL CARCINOMA The classic presentation of oral cavity cancer is an older man who has been aware of a lesion on the lateral border of the tongue for 4-8 months and has a history of heavy smoking and alcohol use. Most common site: Lateral tongue, usually as a painless indurated mass or a non- healing ulcer Other sites: floor of mouth, soft palate, buccal mucosa, labial mucosa and hard palate Variety of clinical presentations: Exophytic (Mass-forming, fungating, papillary) Endophytic (Invasive, burrowing, or ulcerated) Leukoplakic Erythroplakic Erythroleukoplakic Floor of mouth lesions are most likely to arise from a pre-existing leukoplakia or erythroplakia Carcinoma on the gingiva are LEAST associated with tobacco smoking and have the greatest predilection for females Special propensity to mimic benign tumors Oral carcinomas are staged based on TNM criteria (tumor, nodes, metastases) Tumor depth of invasion, size of tumor, and presence of tumor metastases into lymph nodes and distant sites Affects treatment and prognosis  SQUAMOUS CELL CARCINOMA Carcinoma of the lip vermilion is somewhat different from intraoral carcinoma. It has a pathophysiology more akin to squamous cell carcinoma of sun-exposed skin. Slow growing Fewer than 10% of patients have lymph node metastasis Neglect of lesion can result in significant destruction of normal tissue in the area  TUBERCULOSIS Occurs most frequently in middle age adults Oral lesions are usually associated with enlarged regional lymph nodes Common sites for oral TB: tongue, gingiva, mucobuccal fold, areas of inflammation adjacent to teeth or in extraction sites Tuberculosis osteomyelitis has been reported in the jaws and appears as ill-defined areas of radiolucency TB causes delayed hypersensitivity reaction approximately 2-4 weeks after initial exposure This reaction is the basis of PPD skin test  TUBERCULOSIS Histology of Tuberculosis consists of caseating granulomas Granulomas consist of collections epithelioid macrophages Caseating granulomas contain central necrosis “Cheese-like” Multinucleated giant cells may also be seen within granulomas  SARCOIDOSIS Multisystem granulomatous disorder Any organ may be affected but most of unknown cause commonly lungs, lymph nodes, skin, eyes, and Black patients are more affected than salivary glands white patients Facial lesions called “lupus pernio” on nose, Bimodal age distribution. ears, lips, and face First peak: 25-35 years and second peak: 45-65 years  SARCOIDOSIS Any oral mucosal site can be affected The lesion most often is a submucosal mass, an isolated papule, or an area of granularity or an ulceration Lesions may be normal in color, brown-red, or hyperkeratotic Most common site is the buccal mucosa, followed by the gingiva, lips, floor of the mouth, tongue and palate Tx: Corticosteroids are the first line therapy  GRANULOM ATOSIS WITH POLYA NGIIT IS Granulomatous process including lesions of the respiratory tract, necrotizing glomerulonephritis, and systemic vasculitis Thought to be due to abnormal immune reaction in predisposed individual Wide age range: childhood to old age Patients show involvement of the upper and lower respiratory tract  GRANULOMATOSIS WITH POLYANGIITIS Generalized GPA has respiratory tract involvement with rapid development of renal lesions Limited GPA is diagnosed when there is involvement of respiratory system without renal lesions Superficial GPA is one subset of patients that exhibits lesions primarily of the skin and mucosa. In this form systemic involvement develops slowly With progression there is destruction of the nasal septum resulting in saddle nose deformity Saddle nose deformity can also be seen in congenital syphilis, malignant processes, leprosy, and collapse of nasal structures due to drug abuse Symptoms: purulent nasal discharge, chronic sinus pain, congestion, and fever with URI Symptoms: dry cough, hemoptysis, dyspnea or chest pain in LRI Renal involvement usually occur late in the disease and is the most frequent cause of death Oral lesions are seen in the minority of those affected  GPA Most characteristic oral manifestation is ‘Strawberry gingivitis’ Confined classically to the attached gingiva and buccal surfaces Destruction of the underlying bone with the development of tooth mobility has been reported  GRANULOMATOSIS WITH POLYANGIITIS Oral ulcerations may also be a manifestation Lesions are nonspecific and may occur on any mucosal surface Diagnosed in the later stages of the disease with more than 60% of the patients demonstrating renal involvement Treatment: Oral prednisone and cyclophosphamide In my residency, this was considered a “critical diagnosis”  TERTIARY SYPHILIS Gumma: Indurated, nodular, or ulcerative lesion that may produce tissue destruction When the palate is involved the ulceration frequently perforates into the nasal cavity When the tongue is involved usually appears large, lobulated, and irregularly shaped Interstitial glossitis Tx: Intramuscular penicillin administered  FIBROMA AKA Irritation Fibroma, Traumatic Fibroma, Focal Fibrous Hyperplasia, Fibrous Nodule Reactive fibrous hyperplasia in response to local irritation or trauma, not a true neoplasm. Most common on the buccal mucosa at the bite line Some fibromas are fibrous maturation of a pyogenic granuloma Smooth surfaced, pink nodule Can range in size from very small to relatively large Most common in middle aged females  FIBROMA Nodular mass of dense fibrous connective tissue covered by stratified squamous epithelium Overlying epithelium often demonstrates loss of rete ridges Scattered inflammation can be seen Tx: Conservative local excision Submit the excised tissue for microscopic examination because other benign or malignant tumors may mimic the clinical appearance of a fibroma  GIANT CELL FIBROMA Distinctive clinicopathologic features Not associated with trauma Tends to occur at a younger age than a traumatic fibroma 50% of cases appear on the gingiva, the rest can occur on any oral mucosal site Sessile or pedunculated nodule, the surface often appears papillary  RETROCUSPID PAPILLA Developmental lesion that occurs on the gingiva lingual to the mandibular cuspid Identical to giant cell fibroma histologically Reported in 25%–99% of children and young adults Represents a normal anatomic variation that disappears with age If clinically consistent with retrocuspid papillae, no need to biopsy.  GIANT CELL FIBROMA Mass of vascular fibrous connective tissue, which is usually loosely arranged Numerous large, stellate fibroblasts within the superficial connective tissue. These cells may contain several nuclei Often, the surface of the lesion is pebbly The rete ridges may appear narrow and elongated Treatment: conservative surgical excision Exception: Retrocuspid papillae  EPULIS FISSURATUM AKA Inflammatory Fibrous Hyperplasia or Denture epulis Tumor-like hyperplasia of fibrous connective tissue that develops in association with the flange of an ill-fitting complete or partial denture Candidiasis often present, Epulis is a generic term that can be applied to any tumor of the gingiva or alveolar mucosa Single or multiple fold or folds of hyperplastic tissue in the alveolar vestibule The flange of the associated denture fits conveniently into the fissure between the folds. Usually firm and fibrous. Female predilection  THE 3 P’S Differential diagnoses for “Bumps on the Gums” Pyogenic granuloma Peripheral giant cell granuloma Peripheral ossifying fibroma Dr. Stephen Roth oral pathology videos: Honorable mentions: https://youtu.be/srACj910J0w?si=x0OWBeH1D Peripheral fibroma Z3R65wP Peripheral odontogenic fibroma These lesions are reactive, not neoplastic  PYOGE N IC GRANU LOM A (LOBU LAR C APILLARY HE MANGI OM A ) Common tumor-like growth of the oral cavity Exuberant tissue response related to local irritation, poor hygiene, or hormonal factors A misnomer: It is not pyogenic and not a granuloma No longer believed to be related to pyogenic organisms Does not display collections of epithelioid histiocytes Smooth or lobulated mass that is usually pedunculated The surface is characteristically ulcerated and ranges from pink to red to purple Vary from small growths only a few millimeters in size to larger lesions that may measure several centimeters in diameter Typically painless, often bleeds easily, may exhibit rapid growth which may be alarming  PYOGENIC GRANULOMA (LOBULAR CAPILLARY HEMANGIOMA) Striking predilection for the gingiva. Gingival irritation and inflammation that result from poor oral hygiene may be a precipitating factor in many patients. Most common in children and young adults Frequently develop in pregnant women (vascular effects of female hormones), so much so that the terms pregnancy tumor or granuloma gravidarum often are used. May be related to the increasing levels of estrogen and progesterone as the pregnancy progresses.  PERIPHERAL GIANT CELL GRANULOMA A relatively common tumor-like growth of the oral cavity. Occurs exclusively on the gingiva or edentulous alveolar ridge Can be sessile or pedunculated and may or may not be ulcerated. The clinical appearance is similar to the more common pyogenic granuloma (often is more blue-purple compared with the bright red of a typical pyogenic granuloma) “Cupping” resorption of the underlying alveolar bone sometimes is seen On occasion, it may be difficult to determine whether the mass arose as a peripheral lesion or as a central giant cell granuloma that eroded through the cortical plate into the gingival soft tissues. What would help determine whether the lesion is central or peripheral?  PERIPHERAL GIANT CELL GRANULOMA A proliferation of multinucleated giant cells within a background of plump ovoid and spindle-shaped mesenchymal cells Abundant hemorrhage is characteristically found throughout the mass. Tx: Local surgical excision down to the underlying bone. The adjacent teeth should be carefully scaled to remove any source of irritation and to minimize the risk of recurrence.  PERIPHERAL OSSIFYING FIBROMA Occurs exclusively on the gingiva A nodular mass, either pedunculated or sessile, that usually emanates from the interdental papilla Red, ulcerated lesions often are mistaken for pyogenic granulomas; the pink, nonulcerated ones are clinically similar to irritation fibromas. Predominantly a lesion of teenagers and young adults. Predominantly seen in the anterior maxilla of females Rarely, there can be migration and loosening of adjacent teeth  PERIPHERAL OSSIFYING FIBROMA A fibrous proliferation associated with the formation of a mineralized product If the epithelium is ulcerated, then the surface is covered by a fibrinopurulent membrane with a subjacent zone of granulation tissue. The deeper fibroblastic component often is cellular, especially in areas of mineralization. The type of mineralized component is variable and may consist of bone, cementum-like material, or dystrophic calcifications. Frequently, a combination of products is formed. Tx: Local excision excised down to periosteum. Teeth should be thoroughly scaled to eliminate any possible irritants. Periodontal surgical techniques may be necessary to repair the gingival defect esthetically.  TRAUMATIC NEUROMA Not a true neoplasm but a reactive proliferation of neural tissue after transection or other damage of a nerve bundle After a nerve has been damaged, the proximal portion attempts to regenerate and reestablish innervation by the growth of axons through tubes of proliferating Schwann cells. If these regenerating elements encounter scar tissue or otherwise cannot reestablish innervation, then a tumor- like mass may develop at the site of injury. Smooth-surfaced, nonulcerated nodule Most common in the mental foramen area, tongue, and lower lip. Can be associated with altered nerve sensations that can range from anesthesia to dysesthesia to overt pain. Neuromas of the mental nerve are frequently painful, especially when impinged on by a denture or palpated.  TRAUMATIC NEUROMA A haphazard proliferation of nerve bundles Treatment: Surgical excision, including a small portion of the involved proximal nerve bundle. Most lesions do not recur; in some cases, however, the pain persists or returns at a later date.  SCHWANNOMA AKA neurilemmoma A benign neural neoplasm of Schwann cell origin Relatively uncommon, although 25%–48% of all cases occur in the head and neck region A slow-growing, encapsulated tumor that typically arises in association with a nerve trunk. As it grows, it pushes the nerve aside. Usually, the mass is asymptomatic, although tenderness or pain may occur in some instances. The lesion is most common in young and middle-aged adults and can range from a few millimeters to several centimeters in size. On occasion, the tumor arises centrally within bone and may produce bony expansion.  SCHWANNOMA An encapsulated tumor that demonstrates two microscopic patterns in varying amounts: Antoni A: Streaming fascicles of spindle-shaped Schwann cells. These cells often form a palisaded arrangement around central acellular, eosinophilic areas known as Verocay bodies. These Verocay bodies consist of reduplicated basement membrane and cytoplasmic processes. Antoni B: less cellular and less organized; the spindle cells are randomly arranged within a loose, myxomatous stroma. Degenerative changes can be seen in some older tumors (ancient schwannomas). Tx: Surgical excision, and the lesion should not recur  NEUROFIBROMA The most common type of peripheral nerve neoplasm Arises from a mixture of cell types, including Schwann cells and perineural fibroblasts Can arise as solitary tumors or be a component of neurofibromatosis (types I and II) Solitary tumors are most common in young adults and present as slow-growing, soft, painless lesions that vary in size from small nodules to larger masses. The skin is the most frequent location for neurofibromas, but lesions of the oral cavity are not uncommon On rare occasions, the tumor can arise centrally within bone, where it may produce a well- demarcated or poorly defined unilocular or multilocular radiolucency  NEUROFIBROMA Composed of interlacing bundles of spindle-shaped cells that often exhibit wavy nuclei “Leaping dolphins” or “comma- shaped” Mast cells tend to be numerous and can be a helpful diagnostic feature. Tx: local surgical excision, and recurrence is rare. Any patient with a lesion that is diagnosed as a neurofibroma should be evaluated clinically for the possibility of neurofibromatosis  MULTIPLE ENDOCRINE NEOPLASIA (MEN) SYNDROMES Group of rare autosomal dominant conditions characterized by tumors or hyperplasias of the neuroendocrine tissues MEN2 is caused by mutations at various sites of the RET (REarranged during Transfection) proto-oncogene on chromosome 10, which predispose patients to the development of medullary thyroid carcinoma (MTC). Two distinct subtypes are recognized: MEN2A and MEN2B.  In addition to medullary thyroid carcinoma and pheochromocytomas, patients develop multiple mucosal neuromas that especially involve the oral mucous membranes. Usually have a marfanoid body build MULTIPLE ENDOCRINE characterized by thin, elongated limbs with muscle wasting. NEOPLASIA TYPE 2B The face is narrow, but the lips are characteristically thick and protuberant because of the diffuse proliferation of nerve bundles The upper eyelid sometimes is everted because of thickening of the tarsal plate. Small, pedunculated neuromas may be observable on the conjunctiva, eyelid margin, or cornea. Oral mucosal neuromas are usually the first sign of the condition and may be detectable during infancy. Appear as soft, painless papules or nodules that principally affect the lips and anterior tongue Bilateral neuromas of the commissural mucosa are highly characteristic.  MULTIPLE ENDOCRINE NEOPLASIA TYPE 2B Pheochromocytomas of the adrenal glands develop in at least 50% of all patients. The tumor cells secrete catecholamines, which result in symptoms such as profuse sweating, intractable diarrhea, headaches, flushing, heart palpitations, and hypertension. The most significant aspect of this condition is the development of MTC, which occurs in virtually all cases. Medullary thyroid carcinoma is an aggressive tumor that arises from the parafollicular cells (C cells) of the thyroid gland, which are responsible for calcitonin production. Thyroidectomy in first year of life strongly recommended.  MULTIPLE ENDOCRINE NEOPLASIA TYPE 2B Marked hyperplasia of nerve bundles in an otherwise normal or loose connective tissue background. The prognosis for patients with MEN type 2B centers on early recognition of the oral features. Because of the poor prognosis for MTC, the thyroid gland should be removed as soon as possible—preferably within the first year of life. Patients also should be observed for the development of pheochromocytomas because they may result in a life-threatening hypertensive crisis, especially if surgery with general anesthesia is performed.  GRANULAR CELL TUMOR An uncommon benign soft tissue neoplasm that shows a predilection for the oral cavity. Derived from Schwann cells Most common in the oral cavity and on the skin. The single most common site is dorsal tongue. An asymptomatic sessile nodule that is usually 2 cm or less in size Typically pink, but some granular cell tumors appear yellow.  GRANULAR CELL TUMOR Composed of large, polygonal cells with abundant pale eosinophilic, granular cytoplasm. The presence of pseudoepitheliomatous hyperplasia of the overlying epithelium has been reported in up to 50% of all cases. In some cases it may be so striking that it results in a mistaken diagnosis of squamous cell carcinoma and subsequent unnecessary cancer surgery. Treatment: conservative local excision, and recurrence is uncommon  HEMANGIOMAS Infantile hemangiomas are much more common in females than in males The most common location is the head and neck Infantile hemangiomas are rarely present at birth, although a pale macule with threadlike telangiectasias may be noted on the skin. During the first few weeks of life, the tumor will demonstrate rapid development that occurs at a faster pace than the infant's overall growth. Superficial tumors of the skin appear raised and bosselated with a bright-red color (“strawberry” hemangioma). They are firm and rubbery to palpation, and the blood cannot be evacuated by applying pressure. Deeper tumors may appear only slightly raised with a bluish hue. The initial proliferative phase usually lasts for 6–12 months, after which the tumor grows proportionately with the child, followed by slow involution. After tumor regression is complete, normal skin will be restored in about 50% of patients; however, up to 40% of affected individuals will show permanent changes such as atrophy, scarring, wrinkling, or telangiectasias.  VASCULAR MALFORMATIONS Are present at birth and persist throughout life Port wine stains are relatively common capillary malformations. They are most common on the face, particularly along the distribution of the trigeminal nerve. Seen in Sturge-Weber syndrome Port wine stains are typically pink or purple macular lesions that grow commensurately with the patient. As the patient gets older, the lesion often darkens and becomes nodular because of vascular ectasia. Low-flow venous malformations encompass a wide spectrum of lesions, from small isolated ectasias to complex growths that involve multiple tissues and organs. Arteriovenous malformations are high-flow lesions that result from persistent direct arterial and venous communication. Because of the fast vascular flow through these lesions, a palpable thrill or bruit often is noticeable. The overlying skin typically feels warmer to touch.  INTRABONY VASCULAR MALFORMATIONS Usually represent either venous or arteriovenous malformations. In the jaws, such lesions are detected most often during the first three decades of life. Occur three times more often in the mandible than the maxilla Mobility of teeth or bleeding from the gingival sulcus may occur. A bruit or pulsation may be apparent on auscultation and palpation. Most commonly, the lesion shows a multilocular radiolucent defect. The individual loculations may be small (honeycomb appearance) or large (soap bubble appearance). Large malformations may cause cortical expansion, and occasionally a “sunburst” radiographic pattern is produced  S TURGE - WE BE R S YNDRO ME (E NCE PHAL OT R IGE MIN AL ANGIOM ATOSIS) A rare, nonhereditary developmental condition that is characterized by a hamartomatous vascular proliferation involving the tissues of the brain and face. It has been suggested that embryologic mutations result in failure of the primitive cephalic venous plexus to regress and mature properly during the first trimester of pregnan