Oral and Maxillofacial Pathology: Chapter 10: Epithelial Pathology Flashcards

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Human papillomavirus (HPV) comprises a large group of double-stranded DNA viruses, belonging to the family Papillomaviridae. What are four factors assocaited with increased prevalence of oral HPV infection?

  1. male gender
  2. multiple sexual partners
  3. tobacco smoking
  4. HIV infection


Based upon oncogenic potential, mucosal HPV types are categorized as either low-risk or high-risk. What are the two most common high-risk HPV types?

16 and 18


Clinical Features

  • benign, HPV-induced proliferation
  • HPV 6 and 11 identified most commonly
  • predilection for palate, tongue, and lips
  • soft, painless, usually pedunculated, exophytic nodule
  • fingerlike projections impart “cauliflower” appearance
  • enlarges rapidly to a maximum size of about 0.5 cm

Histopathological Features

  • proliferation of keratinized stratified squamous epithelium
  • projections with fibrovascular connective tissue cores
  • koilocytes sometimes are evident high in spinous cell layer

squamous papilloma

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An exophytic lesion of the soft palate with multiple short, white surface projections.

squamous papilloma

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A pedunculated lingual mass with numerous long, pointed, and white surface projections. Note the smaller projections around the base of the lesion.

squamous papilloma

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A pedunculated mass of the buccal commissure, exhibiting short or blunted surface projections and minimal white coloration.

squamous papilloma

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Low-power view showing a pedunculated squamous epithelial proliferation. There are multiple papillary projections with fibrovascular connective tissue cores. A higher power view may reveal koilocytes in the spinous cell layer.

squamous papilloma


What is the most common soft tissue mass arising from the soft palate?

squamous papilloma


What are koilocytes?

Virus-altered epithelial cells with crenated, pyknotic nuclei surrounded by clear halos associated with HPV infection.


What is the treatment and prognosis for squamous papilloma?

  • conservative surgical excision
  • recurrence is unlikely
  • no reported malignant transformation
  • spontaneous remission is possible


Clinical Features

  • focal, benign, HPV-induced hyperplasia
  • HPV 2 is present most often
  • most often arises in children
  • most common on the skin of the hands
  • occur on vermilion border, labial mucosa, or tongue
  • painless papule or nodule
  • papillary projections or a rough, pebbly surface
  • cutaneous lesions may be pink, yellow, or white
  • oral lesions are almost always white
  • enlarge rapidly to its maximum size (usually <5 mm)
  • may form a cutaneous or keratin "horn"

Histopathological Features

  • proliferation of hyperkeratotic stratified squamous epithelium
  • fingerlike, pointed projections with connective tissue cores
  • chronic inflammatory cell infiltrate in supporting connective tissue
  • elongated rete ridges converging toward the center (“cupping”)
  • prominent granular cell layer (hypergranulosis)
  • abundant koilocytes in the superficial spinous layer

verruca vulgaris

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Several warts on the finger, exhibiting a rough, papillary surface. Cutaneous lesions of this type may be pink, yellow, or white.

verruca vulgaris

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Nodular lesion of the skin exhibiting numerous short papillary projections. The skin of the hand is the most common location for this lesion.

verruca vulgaris

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Exophytic, white, papillary lesion of the lateral soft palate. These lesions are most commonly associated with HPV 2.

verruca vulgaris

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  1. Numerous papillary projections are covered by hyperkeratotic stratified squamous epithelium. Elongated rete ridges at the edge of the lesion converge toward the center, producing a "cupping" effect.
  2. High-power view showing clear koilocytes in the upper epithelial layers.

verruca vulgaris


What is the treatment and prognosis for verruca vulgaris?

  • topical salicylic acid, topical lactic acid, or cryotherapy (skin lesions)
  • surgical excision, laser, cryotherapy, or electrosurgery (oral lesions)
  • recurrence is seen in a small proportion of treated cases
  • malignant transformation does not occur
  • two-thirds resolve spontaneously within 2 years


Clinical Features

  • HPV-induced proliferation of the oral and anogenital regions
  • almost all cases attributed to HPV 6 and 11 (90%)
  • usually diagnosed in teenagers and young adults
  • may be an indicator of sexual abuse in young children
  • occur on the labial mucosa and lingual frenum
  • sessile, pink, well-demarcated, nontender, exophytic mass
  • short, blunted surface projections
  • average size is 1.0 to 1.5 cm (can be up to 3 cm)

Histopathological Features

  • benign proliferation of acanthotic stratified squamous epithelium
  • mildly keratotic, papillary surface projections
  • blunted, broader papillary projections with keratin-filled crypts
  • koilocytes within the spinous cell layer

condyloma acuminatum

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Two lesions of the upper lip mucosa exhibit short, blunted projections. These lesions are most commonly associated with HPV 6 and 11.

condyloma acuminatum

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Medium-power photomicrograph showing acanthotic stratified squamous epithelium forming a blunted projection.

condyloma acuminatum

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High-power photomicrograph demonstrating virus-altered epithelial cells with crenated, pyknotic nuclei surrounded by clear halos in the spinous layer.

koilocytes (condyloma acuminatum)


What is the treatment and prognosis for condyloma acuminatum?

  • conservative surgical excision is preferred for oral lesions
  • laser therapy may produce an infectious plume
  • topical agents are a mainstay for anogenital lesions
  • malignant transformation possible for anogenital lesions
  • vaccination recommended for patients 11 to 12 years of age


Clinical Features

  • squamous epithelial proliferation
  • primarily attributed to HPV 13 and 32
  • predominantly arises in children and adolescents
  • most common on labial, buccal, and lingual mucosa
  • pink, smooth-surfaced papules and nodules (papulonodular type)
  • white to pale pink, pebbly nodules (papillomatous type)
  • discrete, well-demarcated lesions 0.1 to 1.0 cm in size
  • may coalesce to produce a cobblestone or fissured appearance

Histopathological Features

  • abrupt and considerable acanthosis of surface epithelium
  • widened, confluent, and club-shaped rete ridges
  • superficial keratinocytes show koilocytic change
  • altered nuclei resembling mitotic figures (mitosoid cells)

multifocal epithelial hyperplasia

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Multiple, flat-topped papules and nodules of normal coloration are seen on the lower lip of a child.

multifocal epithelial hyperplasia

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The lesions may demonstrate a papillary surface change and paleness, as demonstrated on this child's tongue.

multifocal epithelial hyperplasia

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Prominent acanthosis of the epithelium with broad and elongated rete ridges. The slightly papillary surface alteration noted here may or may not be present.

multifocal epithelial hyperplasia

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These cells contain altered nuclei resembling mitotic figures in this otherwise mature and well-differentiated stratified squamous epithelium.

mitosoid cells (multifocal epithelial hyperplasia)


What is the treatment and prognosis for multifocal epithelial hyperplasia?

  • spontaneous regression has been reported
  • conservative surgical excision may be performed
  • cryotherapy, laser, or electrocoagulation
  • recurrence after treatment or regression is possible
  • no malignant transformation potential


Clinical Features

  • sinonasal papilloma variant (18% to 50%)
  • arises almost exclusively on the nasal septum
  • more common in men than women (2 : 1)
  • occurs primarily between 20 to 50 years of age
  • causes unilateral nasal obstruction or epistaxis
  • pink or tan nodule with papillary or warty surface
  • most measure less than 2 cm in maximum diameter

Histopathological Features

  • similar to that of the oral squamous papilloma
  • mucous (goblet) cells and intraepithelial microcysts
  • mitoses are infrequent, and dysplasia is rare

fungiform papilloma

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Erythematous, papillary growth on the nasal septum.

fungiform papilloma


What is the treatment and prognosis for fungiform papilloma?

  • complete surgical excision
  • recurrence of 20% to 30% (may reflect incomplete excision)
  • minimal or no potential for malignant transformation


Clinical Features

  • most common sinonasal papilloma variant (50% to 78%)
  • peaks in fifth and sixth decades (average age, 53 years)
  • arise from the lateral nasal wall or a paranasal sinus
  • cause unilateral nasal obstruction, epistaxis, and discharge
  • soft, pink or tan, polypoid or nodular growth
  • pressure erosion of bone often evident radiographically

Histopathological Features

  • downward proliferation of squamous epithelium into stroma
  • goblet (mucous) cells and mucin-filled microcysts
  • papillary surface projections separated by deep clefts
  • destruction of underlying bone frequently is noted

inverted papilloma

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Magnetic resonance image (MRI) showing a tumor with a characteristic convoluted, cerebriform pattern.

inverted papilloma

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Low-power photomicrograph showing a squamous epithelial proliferation, with multiple “inverting” islands of epithelium extending into the underlying connective tissue.

inverted papilloma


What is the treatment and prognosis for inverted papilloma?

  • transnasal endoscopic surgery
  • recurrence rates of 13% to 17% or less
  • approximately 3% to 24% transform into malignancy


Clinical Features

  • most often occurs in adults older than 50 years
  • predilection for lateral nasal wall, antrum, and ethmoid sinus
  • commonly presents as unilateral nasal obstruction
  • beefy-red or brown mass with a multinodular surface

Histopathological Features

  • endophytic and exophytic growth
  • lesional epithelial cells similar to oncocytes
  • intraepithelial microcysts filled with mucin or neutrophils

cylindrical cell papilloma


What is the treatment and prognosis for cylindrical cell papilloma?

  • treatment and recurrence similar to inverted papilloma
  • malignant transformation rates from 4% to 17%


Clinical Features

  • induced by molluscum contagiosum virus (MCV)
  • mainly arises in children and young adults
  • occur predominantly on neck, face, trunk, and genitalia
  • occur orally on the lips, buccal mucosa, palate, or gingiva
  • clustered, pink or white, smooth-surfaced, sessile papules
  • measure 2 to 4 mm in diameter
  • central plug expresses curd-like substance
  • mostly asymptomatic, but tenderness or pruritus possible

Histopathological Features

  • localized, lobular proliferation of stratified squamous epithelium
  • bloated keratinocytes containing Henderson-Paterson bodies
  • central crater is formed by disintegrating stratum corneum cells

molluscum contagiosum

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Multiple, smooth-surfaced papules, with several demonstrating small keratin-like plugs, are seen on the neck of a child.

molluscum contagiosum

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Well-defined epidermal proliferation demonstrating a central craterlike depression filled with virally altered keratinocytes.

molluscum contagiosum

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Higher-power photomicrograph showing the large, intranuclear, basophilic viral inclusions of keratinocytes being sloughed into the central crater.

molluscum (or Henderson-Paterson) bodies (molluscum contagiosum)


What is the treatment and prognosis for molluscum contagiosum?

  • most cases undergo spontaneous remission within 6 to 9 months
  • lesions most commonly are removed by curettage or cryotherapy
  • cidofovir may be effective in immunosuppressed patients
  • recurrence has been reported in up to one-third of patients
  • no apparent malignant transformation potential


Clinical Features

  • typically is seen in white males, 40 to 70 years of age
  • intraoral lesions occur on gingiva and alveolar mucosa
  • well-demarcated, soft, painless, sessile, slightly elevated mass
  • white, yellow-white, or red color
  • papillary or verruciform surface
  • most are smaller than 2 cm

Histopathological Features

  • papillary, acanthotic surface epithelium
  • thickened layer of parakeratin, often with a distinct orange color
  • parakeratin-filled crypts between epithelial projections
  • large macrophages with foamy, lipid-laden cytoplasm

verruciform xanthoma

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A well-demarcated, slightly elevated lesion of the hard palate that demonstrates a roughened or papillary surface.

verruciform xanthoma

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A lesion of the ventral tongue exhibits a biphasic appearance. The anterior aspect demonstrates elongated white (well-keratinized) projections. The posterior aspect demonstrates a surface of yellow, blunted projections.

verruciform xanthoma

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  1. A slight papillary appearance is produced by hyperparakeratosis, and the rete ridges are elongated to a uniform depth. Note the orange-colored parakeratin plugging between the papillary projections.
  2. The connective tissue papillae are composed almost exclusively of large macrophages with foamy, lipid-laden cytoplasm (xanthoma cells).

verruciform xanthoma


What is the treatment and prognosis for verruciform xanthoma?

  • conservative surgical excision
  • recurrence is rare
  • no malignant transformation has been reported


Clinical Features

  • common benign proliferation of epidermal basal cells
  • positive correlation with chronic sun exposure
  • does not occur in the mouth
  • develop on the skin of the face, trunk, and extremities
  • occur in fourth decade and become more common with age
  • multiple, beginning as small, tan to brown macules
  • clinically indistinguishable from actinic lentigines
  • form sharply demarcated plaques with "stuck on" appearance
  • finely fissured, pitted, verrucous, or smooth surfaces
  • usually less than 2 cm in diameter
  • sometimes indicate internal malignancy (Leser-Trélat sign)

Histopathological Features

  • exophytic proliferation of basilar epithelial cells
  • surface keratinization, acanthosis, and papillomatosis
  • epithelial hyperplasia above normal epidermal surface
  • keratin-filled, cystic-appearing invaginations ("horn cysts")
  • melanin pigmentation within basal layer
  • acanthosis with minimal keratinization (acanthotic form)
  • hyperkeratosis with minimal acanthosis (hyperkeratotic form)
  • anastomosing trabeculae of lesional cells (adenoid form)
  • epithelial metaplasia results in whorled patterns ("squamous eddies")

seborrheic keratosis

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Multiple brown plaques on the face of an older man exhibit a fissured surface. They had been slowly enlarging for several years.

seborrheic keratosis

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Crusted and pigmented epidermal plaque. These lesions are clinically indistinguishable from actinic lentigines.

seborrheic keratosis

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The acanthotic form demonstrates considerable acanthosis, surface hyperkeratosis, and numerous pseudocysts. The epidermal proliferation extends upward, above the normal epidermal surface.

seborrheic keratosis

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Pseudocysts are actually keratin-filled invaginations, as seen toward the left in this high-power photomicrograph. The surrounding epithelial cells are basaloid in appearance.

seborrheic keratosis


Clinical Features

  • form of seborrheic keratosis
  • occurs in approximately 30% to 77% of blacks
  • frequently has an autosomal dominant inheritance pattern
  • multiple small (1 to 4 mm), dark-brown to black papules
  • found in the zygomatic and periorbital regions

dermatosis papulosa nigra

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Multiple small pigmented papules of the malar area. These leisons are considered to be a form of seborrheic keratosis.

dermatosis papulosa nigra


Sudden appearance of numerous seborrheic keratoses with pruritus may be associated with internal malignancy. What is this called?

Leser-Trélat sign


What is the treatment and prognosis for seborrheic keratosis?

  • seldom removed except for aesthetic concerns or irritation
  • cryotherapy, curettage, or shave excision
  • no appreciable malignant potential


Clinical Features

  • localized proliferation of sebaceous glands
  • usually affects adults older than 40 years
  • most common on the skin of the face
  • one or more soft, nontender papules
  • white, yellow, or normal color
  • most grow slowly and are smaller than 5 mm
  • usually exhibit central umbilication
  • can express sebum (unlike basal cell carcinoma)

Histopathological Features

  • enlarged but otherwise normal sebaceous gland lobules
  • one or more centrally located sebaceous ducts

sebaceous hyperplasia

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Multiple soft papules of the midface are umbilicated and small. Sebum can often be expressed from the central depressed area.

sebaceous hyperplasia

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Sebaceous glands are enlarged and more numerous than normal, but they demonstrate no other pathologic changes.

sebaceous hyperplasia


What is the treatment and prognosis for sebaceous hyperplasia?

  • no treatment is necessary
  • excisional biopsy is curative


Clinical Features

  • common hyperpigmented macule of the skin
  • become more pronounced after sun exposure
  • closely associated with history of painful sunburns
  • arise most often on the face, arms, and back
  • occur in fair-skinned individuals
  • sharply demarcated, uniformly light brown, macules
  • less than 3 mm in diameter
  • great variability in number
  • lighter color than lentigo simplex
  • never elevated like melanocytic nevus

Histopathological Features

  • abundant melanin deposition in the basal cell layer
  • melanocyte number normal or slightly reduced
  • no elongation of rete ridges

ephelides ("freckles")

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Multiple brown macules over the bridge of the nose. Note these these have a lighter brown color and are flat, not raised.



What is the treatment and prognosis for ephelides?

  • no treatment is necessary except for cosmetic reasons
  • cryotherapy, hydroquinone, chemical peels, or laser therapy
  • sunscreens prevent new lesions and reduce darkening of existing lesions


Clinical Features

  • hallmark of photodamaged skin
  • associated with both chronic and intermittent UV exposure
  • does not occur in the mouth
  • affects more than 90% of whites older than 70 years
  • occur on sun exposed skin (face, hands, forearms, upper back)
  • uniformly pigmented, brown to tan macules
  • well-demarcated but irregular borders
  • most are smaller than 5 mm, but some are more than 1 cm
  • no change in color after UV light exposure, unlike ephelides

Histopathological Features

  • club-shaped, elongated rete ridges
  • thinning of epithelium above connective tissue papillae
  • melanin-laden basilar cells
  • excessive numbers of heavily pigmented melanocytes
  • prominent solar elastosis within the dermis

actinic lentigo

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Multiple lesions on the sun-exposed skin of the hand of an older adult. Lesions are brown macules with irregular borders.

actinic lentigo

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Large, flat, evenly pigmented lesion on the forehead of an older adult man. This lesion would not darken in color after sun exposure.

actinic lentigo

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Rete ridges are elongated and occasionally intertwining. Pigmented melanocytes (with clear cytoplasm) are excessive and commingled with melanin-laden basilar cells.

actinic lentigo


What is the treatment and prognosis for actinic lentigo?

  • no treatment is necessary except for cosmetic reasons
  • cryotherapy, laser therapy, intense pulsed light, or chemical peels
  • topical therapies (hydroquinone, tretinoin, tazarotene, adapalene)
  • sunscreen recommended as preventive treatment
  • rarely recur after removal, although new lesions may arise
  • no malignant transformation, but is clinical marker of photodamage


Clinical Features

  • benign cutaneous melanocytic hyperplasia of unknown cause
  • typically found on skin not exposed to sunlight
  • darker color than ephelis, but do not darken with sun exposure
  • usually is seen in children
  • sharply demarcated, uniformly tan to dark-brown macule
  • clinically indistinguishable from non-elevated melanocytic nevus

Histopathological Features

  • increased number of benign melanocytes within basal layer
  • abundant melanin among melanocytes and basal keratinocytes
  • melanophages within the papillary dermis (melanin incontinence)

lentigo simplex

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A sharply demarcated lesion of uniform brown coloration is seen on the midface, clinically indistinguishable from non-elevated melanocytic nevus.

lentigo simplex


What is the treatment and prognosis for lentigo simplex?

  • may fade spontaneously after many years
  • treatment not required, except for cosmetic reasons
  • conservative surgical excision, cryotherapy, and laser therapy
  • no malignant transformation potential


Clinical Features

  • symmetrical hyperpigmentation of sun-exposed skin
  • classically associated with pregnancy
  • commonly affects medium- to dark-complexioned persons
  • typically appears in adult women, rarely affects men
  • bilateral brown or grayish cutaneous macules
  • range from a few millimeters to more than 2 cm
  • may remain faint or darken over time

Histopathological Features

  • increased melanin deposition in the epidermis
  • possibly increased numbers of melanocytes
  • numerous melanophages may be seen in the dermis


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Diffuse hyperpigmentation of the facial skin in a pregnant woman. UV light exposure and hormonal influences appear to be important etiologic factors.



What is the treatment and prognosis for melasma?

  • triple-combination cream (hydroquinone, tretinoin, fluocinolone)
  • dual- or single-agent topicals available for patients with sensitivities
  • sun avoidance, protective clothing, and sunscreens for management
  • may resolve after parturition or after discontinuing oral contraceptives
  • no potential for malignant transformation


Clinical Features

  • focal increase in melanin deposition
  • occurs over a broad age range (average age, 43 years)
  • more common in females (2 : 1)
  • occur on lip vermillin (33%), buccal mucosa, gingiva, palate
  • solitary, well-demarcated, round to oval macule
  • uniformly tan to dark-brown
  • asymptomatic
  • diameter of 7 mm or less
  • dependent on sun exposure (unlike ephelis)

Histopathological Features

  • increase in melanin in basal and parabasal layers
  • otherwise normal stratified squamous epithelium
  • melanin be free in subepithelial tissue (melanin incontinence)
  • does not show elongated rete ridges

oral melanotic macule

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A single small, uniformly pigmented brown macule on the lower lip vermilion.

oral melanotic macule

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A well-demarcated brown macule of the gingival mucosa.

oral melanotic macule

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  1. Low-power view showing increased melanin pigmentation distributed along basal epithelial layer.
  2. High-power view showing granular brown melanin pigment in the basilar cells.

oral melanotic macule


What is the treament and prognosis for oral melanotic macule?

  • generally benign, but early melanoma presents similarly
  • all oral pigmented macules should be submitted
  • excisional biopsy is preferred
  • similar lesions may be caused by certain diseases or medications


Clinical Features

  • uncommon, benign, acquired pigmentation of oral mucosa
  • seen primarily in blacks and females
  • most commonly arises during the third and fourth decades
  • occur on the buccal mucosa, lips, palate, and gingiva
  • typically asymptomatic, but pain, burning, or pruritus may occur
  • smooth, flat or slightly raised, and dark-brown to black
  • rapidly increase in size, and may reach several centimeters

Histopathological Findings

  • numerous benign dendritic melanocytes throughout epithelium
  • increased numbers of basal layer melanocytes
  • spongiosis and mild acanthosis typically evident
  • mild to moderate chronic inflammatory cell infiltrate

oral melanoacanthoma

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  1. Smooth, darkly pigmented macule of the buccal mucosa in a young adult.
  2. Appearance of the lesion 2 months later showing dramatic enlargement.
  3. Resolution of the lesion 3 months after incisional biopsy.

oral melanoacanthoma

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Medium-power photomicrograph showing acanthosis of the epithelium. Spongiosis is demonstrated by intercellular spaces between the keratinocytes.

oral melanoacanthoma

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High-power view showing numerous dendritic melanocytes extending between the spinous epithelial cells. These are normally confined to the basal layer.

oral melanoacanthoma


What is the treatment and prognosis for oral melanoacanthoma?

  • incisional biopsy usually is indicated to rule out melanoma
  • recurrence or development of additional lesions is rare
  • no potential for malignant transformation


What term refers to congenital or developmental malformations of the skin (and mucosa)?



Clinical Features

  • benign, localized proliferation of nevus cells
  • most common human “tumor”
  • associated with BRAF mutations (80%)
  • four stages: initiation, promotion, senescence, involution
  • begin developing during childhood
  • more common in men than in woman
  • more common in whites than in blacks
  • most occur in head and neck region, rarely intraorally
  • can occur on palate, mucobuccal fold, gingiva
  • sharply demarcated, brown or black macule (junctional)
  • elevated, soft papule with smooth surface (compound)
  • papillomatous, with hairs growing (intradermal)
  • usually remain less than 6 mm

Histopathologic Features

  • benign, unencapsulated proliferation of nevus cells
  • superficial cells organized in aggregates (thèques)
  • deeper cells appear much like lymphocytes
  • deepest cells appear elongated and spindle-shaped
  • nevus cells confined to epithelium (junctional)
  • nevus cells within connective tissue (compound)
  • nevus cells only in connective tissue (intradermal)

acquired melanocytic nevus

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A brown nodule on the facial skin with a papillomatous surface and protruding hairs.

intradermal melanocytic nevus

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A well-demarcated, lightly pigmented, dome-shaped papule is seen at the edge of the vermilion border of the upper lip.

intradermal melanocytic nevus

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Pigmented lesion of the anterior hard palate. Intraoral lesions of this type are are distinctly uncommon.

intramucosal melanocytic nevus

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This lesion of the mandibular gingiva is nonpigmented. More than one in five intraoral lesions of this type lack clinical pigmentation.

intramucosal melanocytic nevus

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Nests of melanocytic nevus cells along the basal layer of the epithelium. This is in the early stage of this lesion.

junctional melanocytic nevus

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High-power view showing nests of pigmented nevus cells within the epithelium and the superficial lamina propria. This is a later stage of the lesion.

compound melanocytic nevus

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Collections of melanocytic nevus cells are only within the lamina propria. This is the latest stage of the lesion.

intradermal melanocytic nevus


What is the treatment and prognosis for melanocytic nevus?

  • no treatment indicated except for cosmetic reasons or irritation
  • cutaneous lesions regress in midlife; few remain by 90 years
  • if removal is elected, then conservative surgical excision
  • recurrence is unlikely
  • low risk of malignant transformation


Clinical Features

  • occur on the trunk and extremities of newborns
  • intraoral involvement is rare
  • small (<1.5 cm), medium (1.5 to 20 cm) or large (≥20 cm)
  • initially medium to large light tan macules
  • develop into dark rough-surfaced plaques
  • hypertrichosis becoming more prominent with age
  • some can be very large ("bathing trunk" or "garment")

Histopathologic Features

  • similar to acquired melanocytic nevus (possibly indistinguishable)
  • composed of nevus cells
  • may have a junctional, compound, or intradermal pattern
  • often extends into deeper levels of the dermis

congenital melanocytic nevus

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Pigmented lesion of the skin showing hypertrichosis. This feature of the lesion may become more prominent with age.

congenital melanocytic nevus

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Deeply pigmented lesion of the lingual mandibular gingiva in a 3-year-old child. Intraoral lesions of this type are rare.

congenital melanocytic nevus


What is the treatment and prognosis for congenital melanocytic nevus?

  • many are excised for aesthetic purposes
  • complete excision may not be feasible for large lesions
  • dermabrasion, laser therapy, cryotherapy, or chemical peels
  • approximately 2% to 3% transform into malignant melanoma
  • giant or multiple lesions are risk for neurocutaneous melanosis


Clinical Features

  • melanocytic nevus with a hypopigmented border
  • melanocyte destruction by the immune system
  • develops from preexisting acquired melanocytic nevi
  • most common on the skin of the trunk
  • occurs during second decade of life
  • pigmented papule or macule
  • hypopigmented border, 2 to 3 mm or wider

Histopathologic Features

  • similar to acquired melanocytic nevus
  • intense chronic inflammatory cell infiltrate

halo nevus

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Elevated brown lesion of the skin showing surrounding depigmentation.

halo nevus


What is the treatment and prognosis for halo nevus?

  • most regress and do not require treatment
  • if treatment is elected, conservative surgical removal is curative
  • recurrence is unlikely


Clinical Features

  • uncommon melanocytic nevus variant
  • develop on extremities or face during childhood
  • solitary, dome-shaped papule
  • pink to reddish-brown
  • usually smaller than 6 mm
  • age at presentation and size distinguish from melanoma

Histopathologic Features

  • shares many features with melanoma
  • spindle-shaped or plump epithelioid cells
  • solitary or coalescent eosinophilic globules
  • ectatic blood vessels and normal mitotic figures

Spitz nevus


What is the treatment and prognosis for Spitz nevus?

  • conservative surgical excision
  • low chance of recurrence


Clinical Features

  • benign proliferation of dermal melanocytes
  • two major types: common and cellular
  • predilection for dorsal hands and feet, scalp, and face
  • oral lesions almost always are found on palate
  • occurs in children and young adults
  • exhibits a female predilection
  • macular or dome-shaped, blue or blue-black lesion
  • smaller than 1 cm in diameter

Histopathologic Features

  • slender melanocytes with extensions and granules (common)
  • plump, melanin-producing spindle cells (cellular)
  • cells are located deep within the dermis or lamina propria

blue nevus

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A well-circumscribed, deep-blue macular lesion is seen on palatal mucosa.

blue nevus

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  1. Abundant melanin is seen within spindle-shaped melanocytes located relatively deep within the lamina propria and parallel to the surface epithelium.
  2. High-power view showing heavily pigmented spindle-shaped cells.

blue nevus


The blue color of blue nevi can be explained by the Tyndall effect. What is the Tyndall effect?

Colors with long wavelengths (red) tend to be absorbed more readily by tissue, while shorter-wavelengths (blue) are more likely to be reflected.


What is the treatment and prognosis for blue nevus?

  • conservative surgical excision
  • recurrence is minimal
  • malignant transformation is possible, but rare
  • biopsy of intraoral pigmented lesions is usually advisable


A white patch or plaque that cannot be characterized clinically or pathologically as any other disease.



A benign, morphologically altered tissue that has a greater than normal risk of malignant transformation.

precancerous lesion


A disease or patient habit that does not necessarily alter the clinical appearance of local tissue but is associated with a greater than normal risk of precancerous lesion or cancer development in that tissue.

precancerous condition


A lesion, disease, or condition associated with a greater than normal risk of developing malignancy.

potentially malignant disorder


The risk of cancer being present in a precancerous lesion or condition, either at initial diagnosis or in the future (usually expressed in percentages).

malignant transformation potential


A specific epidemiologic measure of the association between exposure to a particular factor and the risk of acquiring a disease, expressed as a ratio of the incidence or prevalence of a disease among those exposed and those not exposed to the factor.

relative risk


What is the most common oral precancer?



The cause of leukoplakia remains unknown, although hypotheses abound. What are six factors associated with the development of leukoplakia?

  1. tobacco use
  2. alcohol consumption
  3. sanguinaria
  4. ultraviolet radiation
  5. microorganisms
  6. trauma

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Thin white plaque on the maxillary alveolar mucosa. This patient reported using Viadent toothpaste and mouthwash.

sanguinaria-associated keratosis

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  1. Well-circumscribed red and white plaque on the anterior floor of mouth, which showed fungal infestation on cytology smears.
  2. After antifungal therapy, the erythematous component resolved, resulting in a homogeneous white plaque.

candidal leukoplakia

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There is a rough, hyperkeratotic change to the posterior mandibular alveolar ridge, because this area is now edentulous and becomes traumatized from mastication.

frictional keratosis


Clinical Features

  • usually affects persons older than 40 years
  • prevalence increases rapidly with age
  • occur on lip vermilion, buccal mucosa, gingiva
  • flat to slightly elevated, gray or white plaque
  • may be somewhat translucent, fissured, or wrinkled
  • may demonstrate scattered patches of redness (erythroplakia)

Histopathological Features

  • thickened keratin layer of the surface epithelium (hyperkeratosis)
  • may have thickened spinous layer (acanthosis)
  • hyperkeratosis may consist of parakeratin, orthokeratin, or both
  • may exhibit dysplasia or carcinoma (5% to 25%)
  • dysplastia typically begins in basilar and parabasilar portions


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A diffuse, corrugated white patch on the right ventral surface of the tongue and floor of mouth. This represents a later stage of the lesion that is especially prevalent in tobacco smokers.

homogeneous or thick leukoplakia

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Extensive buccal mucosal lesion with uneven whiteness and fissures. Moderate epithelial dysplasia was noted on histopathologic evaluation, and squamous cell carcinoma later developed in this area.

homogeneous or thick leukoplakia

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Focal lesion with a rough, granular surface on the posterior lateral border of the tongue. Biopsy revealed early invasive squamous cell carcinoma.

granular or nodular leukoplakia


Clinical Features

  • special high-risk form of leukoplakia
  • multiple, slowly spreading, keratotic plaques
  • rough surface projections
  • may be indistinguishable from verrucous carcinoma
  • many transform into squamous cell carcinoma
  • strong female predilection (4 : 1)
  • minimal association with tobacco use

proliferative verrucous leukoplakia (PVL)

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  1. Diffuse, corrugated, white lesions of the buccal and palatal mucosa.
  2. Thickened, corrugated, white lesion involving the palate, alveolar ridge, and lingual marginal gingiva.

proliferative verrucous leukoplakia (PVL)

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  1. An elderly white female developed extensive leukoplakia with rough surface projections on the buccal mucosa and mandibular alveolar ridge.
  2. After failing to comply with a recommendation for biopsy, the same patient returned 2 years later with a verrucous carcinoma.

proliferative verrucous leukoplakia (PVL)

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Red and white lesion of the lateral border of the tongue. Biopsy revealed carcinoma in situ.


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Extensive ventral and lateral tongue lesion with areas representing various possible phases or clinical appearances.



Many leukoplakic lesions are a mixture of phases or subtypes. Ideally, where should biopsies of such mixed lesions be taken from?

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Biopsies should be taken from areas of a lesion most likely to harbor dysplasia or carcinoma (i.e. towards the right of the figure).

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What type of kerotosis is shown in this figure?

The left shows hyperorthokeratosis with a well-defined granular cell layer. The right shows normal parakeratinized epithelium without a granular cell layer.


The more dysplastic the epithelium becomes, the more the atypical epithelial changes extend to involve the entire thickness of the epithelium. What are typical histopathologic alterations of dysplastic epithelial cells? (12)

Visible at high-power magnification:

  1. enlarged nuclei and cells
  2. large and prominent nucleoli
  3. increased nuclear-to-cytoplasmic ratio
  4. hyperchromatic (excessively dark-staining) nuclei
  5. pleomorphic (abnormally shaped) nuclei and cells
  6. dyskeratosis (premature keratinization of individual cells)
  7. increased mitotic activity (excessive numbers of mitoses)
  8. abnormal mitotic figures (tripolar or star-shaped mitoses)

Visible at low-power magnification:

  1. bulbous or teardrop-shaped rete ridges
  2. loss of polarity (lack of progressive maturation)
  3. keratin or epithelial pearls (concentric keratinized cells)
  4. loss of typical epithelial cell cohesiveness


The grade of epithelial dysplasia refers to its “severity” or intensity. What are the four grades of epithelial dysplasia?

  1. mild dysplasia is limited to basal and parabasal layers
  2. moderate dysplasia extends to the mid spinous layer
  3. severe dysplasia exends above the midpoint of the epithelium
  4. carcinoma in situ involves the entire thickness of the epithelium

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Hyperchromatic and slightly pleomorphic nuclei are noted in the basal and parabasal cell layers of this stratified squamous epithelium.

mild dysplasia

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Dysplastic changes extend to the midpoint of the epithelium and are characterized by nuclear hyperchromatism, pleomorphism, and cellular crowding.

moderate dysplasia

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Epithelium exhibiting marked pleomorphism, hyperchromatism, and scattered mitotic figures. Atypical cells involve most of the epithelial thickness.

severe dysplasia

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Salivary gland duct exhibiting squamous metaplasia and dysplasia that originated from an overlying surface epithelial dysplasia.

ductal dysplasia

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Dysplastic changes extend throughout the entire thickness of the epithelium. An important feature is absence of invasion; metastasis cannot occur.

carcinoma in situ


What is the treatment and prognosis for leukoplakia?

  • biopsy is required to obtain a histopathologic diagnosis
  • moderate epithelial dysplasia or worse warrants removal
  • milder dsyplasia may respond to conservative measures
  • surgical excision, electrocautery, cryosurgery, or laser ablation
  • recurrence rates range from 10% to 35%
  • malignant transformation rate of less than 2%
    • 2% to 7% of homogeneous or thick
    • 4% to 15% of granular or verruciform
    • 28% of erythroleukoplakia
    • 4% to 11% for moderate dsyplasia
    • 20% to 43% for severe dsyplasia


A red patch or plaque that cannot be clinically or pathologically diagnosed as any other condition.



Clinical Features

  • peak prevalence of 65 to 74 years
  • occurs on floor of mouth, tongue, and soft palate
  • well-demarcated, erythematous patch or plaque
  • soft, velvety texture
  • usually asymptomatic
  • may be associated with leukoplakia

Histopathology Features

  • 90% represent severe dysplasia, CIC, or SCC
  • atropic epithelium lacking keratin production (red color)
  • chronic inflammation of underlying connective tissue


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Erythematous macule on the right floor of the mouth. Biopsy showed early invasive squamous cell carcinoma.


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Well-circumscribed red patch on the posterior lateral hard and soft palate.



What is the treatment and prognosis for erythroplakia?

  • biopsy should be performed on all red lesions of oral mucosa
  • if there is a source of irritation, biopsy can be delayed for 2 weeks
  • moderate dysplasia or worse typically warrants complete excision
  • recurrence and multifocal involvement are common


Clinical Features

  • painless gingival recession
  • characteristic white or gray plaque
  • mucosa is thin and translucent
  • may feel soft and velvety
  • stretching mucosa reveals a “pouch”
  • usually develops over 1 to 5 years
  • may become leathery or nodular

Histopathological Features

  • hyperkeratotic and acanthotic squamous epithelium
  • parakeratin chevrons within superficial epithelium
  • unusual deposition of amorphous eosinophilic material

smokeless tobacco keratosis

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Extensive recession of the anterior mandibular facial gingiva.

smokeless tobacco-related gingival recession

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A soft, fissured, gray-white lesion of the lower labial mucosa located in the area of chronic snuff placement. The gingival melanosis is racial pigmentation.

tobacco pouch keratosis (mild)

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A somewhat leathery, white, fissured plaque of the right mandibular vestibule, which was located in the area of chronic chewing tobacco placement.

tobacco pouch keratosis (severe)

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Epithelium exhibiting acanthosis, hyperparakeratosis, and “chevron” formation.

tobacco pouch keratosis

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  1. Low-power view showing mild hyperkeratosis and acanthosis. Note linear deposition of amorphous, eosinophilic material in the lamina propria above the minor salivary glands.
  2. Higher-power view of the amorphous material.

tobacco pouch keratosis


What is the treatment and prognosis for tobacco pouch keratosis?

  • biopsy is needed for only severe or atypical lesions
  • may only require monitoring and tobacco cessation
  • any lesions that remain after 6 weeks of cessation should be biopsied

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  1. Moderately severe lesion of the lower anterior vestibule and lip in a 15-year-old male. There is a gray-white, fissured surface. The patient had placed snuff in the area for several years.
  2. Two weeks after cessation of the tobacco habit, the mucosa returned to an almost normal appearance.

tobacco pouch keratosis


Clinical Features

  • high-risk, precancerous condition
  • chronic, progressive scarring of oral mucosa
  • linked to the use of betel quid (paan)
  • often manifests in young adults
  • chief complaints of trismus and stomatopyrosis
  • occurs on buccal mucosa, retromolar area, and soft palate
  • blotchy, marblelike pallor and progressive stiffness
  • leukoplakia often noted

Histopathological Features

  • densely collagenized, hypovascular connective tissue
  • variable numbers of chronic inflammatory cells
  • ragged keratinaceous surface covered by betel quid ingredients

oral submucous fibrosis

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Pallor and fibrosis of the soft palate in a betel quid chewer. The uvula has retained its normal color.

oral submucous fibrosis

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Mucosal biopsy exhibiting hyperparakeratosis, basilar hyperplasia, and fibrosis in the lamina propria.

oral submucous fibrosis


What is the treatment and prognosis for oral submucous fibrosis?

  • unlike tobacco pouch keratosis, does not regress with cessation
  • mild cases may be treated with intralesional corticosteroids
  • moderate to severe cases may require surgical excision
  • relapse is common
  • malignant transformation rate of 8%
  • 19 times more likely to develop oral cancer


Clinical Features

  • most commonly affects men older than 45 years
  • palatal mucosa becomes diffusely gray or white
  • slightly elevated papules with punctate red centers
  • may thicken into a fissured, “dried mud” appearance
  • heavy tobacco stain is often present on the teeth

Histopathological Features

  • hyperkeratosis and acanthosis of palatal epithelium
  • chronic inflammation of subepithelial connective tissue
  • squamous metaplasia of the excretory ducts
  • inflammatory exudate may be noted within the duct lumina

nicotine stomatitis

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This extensive leathery, white change of the hard palate in a pipe smoker is sprinkled throughout with numerous red papules, which represent inflamed salivary duct openings. The gingival mucosa also is keratotic.

nicotine stomatitis

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Close-up of the inflamed ductal openings of involved salivary glands of the hard palate. Note the white keratotic ring at the lip of many of the inflamed ducts.

nicotine stomatitis

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There is hyperkeratosis and acanthosis of the palatal epithelium. Note the squamous metaplasia of the minor salivary gland ducts.

nicotine stomatitis


What is the treatment and prognosis of nicotine stomatitis?

  • completely reversible, even when it has been present for decades
  • usually returns to normal within 1 to 2 weeks of smoking cessation
  • any lesions that persist after 1 month cessation should be biopsied


Clinical Features

  • common, cutaneous premalignant lesion
  • caused by chronic, high-level exposure to UV radiation
  • affects more than 50% of white adults with sun exposure
  • occurs on face, neck, hands, forearms, and balding scalp
  • often occur in clusters of irregular, scaly plaques
  • range in color from normal to white, gray, or brown
  • palpation reveals a rough, “sandpaper-like” texture
  • usually smaller than 7 mm, may reach 2 cm or more
  • may produce a central keratin “horn"

Histopathological Features

  • hyperparakeratosis and acanthosis
  • teardrop-shaped rete ridges
  • epithelial dysplasia is present
  • band of pale, basophilic connective tissue (solar elastosis)

actinic keratosis


What is solar elastosis?

A UV light–induced alteration of collagen and elastic fibers that appears histologically as a band of amorphous, acellular, basophilic connective tissue underlying the epithelium.

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A plaque of the skin of the face with a rough, sandpaper-like surface.

actinic keratosis

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  1. An extremely excessive amount of parakeratin is noted on the epidermal surface.
  2. High-power view showing hyperchromatism and pleomorphism of the epidermal cells.

actinic keratosis


What is the treatment and prognosis of actinic keratosis?

  • prevention with avoiding sun exposure and using sunscreen
  • for solitary lesions, the most common treatment is cryotherapy
  • multifocal lesions require topical agents, chemical peels, laser therapy
  • recurrence is rare, but additional lesions frequently arise
  • low malignant potential


Clinical Features

  • common premalignant alteration of lower lip vermilion
  • results from chronic UV light exposure
  • associated with outdoor occupations ("farmer's lip")
  • seldom occurs in persons younger than 45 years
  • strong male predilection (as much as 10 : 1)
  • develops slowly (patients often unaware)
  • first appears as blurring of the lower lip vermilion
  • as it progresses, rough, scaly areas develop
  • may thicken into leukoplakic lesions
  • eventually chronic ulceration may develop

Histopathological Features

  • varying degrees of dysplasia
  • hyperkeratosis, and either atrophic or acanthotic
  • band of pale, basophilic connective tissue (solar elastosis)

actinic cheilosis

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Diffuse, irregular white plaque at the wet line of the lower lip vermilion. This represents an earlier stage of the lesion.

actinic cheilosis

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Crusted and ulcerated lesions of the lower lip vermilion. This represents a later stage of the lesion.

actinic cheilosis

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Patient with actinic cheilosis of the lower lip, who developed a small, chronic ulceration.

squamous cell carcinoma arising in actinic cheilosis

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Hyperorthokeratosis and epithelial atrophy. Note the striking underlying solar elastosis.

actinic cheilosis


What is the treatment and prognosis for actinic cheilosis?

  • reduce sun exposure to prevent further damage
  • indurated, thickened, or ulcerated lesions should be biopsied
  • lip shave procedure (vermilionectomy) may be performed
  • doubles risk for developing squamous cell carcinoma of the lip


Clinical Features

  • self-limiting ("self-healing"), epithelial proliferation
  • hereditary predisposition for multiple lesions
  • male predilection
  • rarely occurs before 45 years of age
  • involve sun-exposed skin (95%)
  • firm, well-demarcated, sessile, dome-shaped nodule
  • yellowish, brown, or black crusted central plug of keratin
  • mostly asymptomatic, but pruritus and tenderness possible
  • three phases: growth, stationary, involution

Histopathological Features

  • similar to well-differentiated squamous cell carcinoma
  • central crater filled with keratin
  • “buttressing” between epithelium and lesion
  • downward proliferation of epithelium at crater base


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A nontender, well-demarcated nodule of the skin of the nose in an older woman. The nodule demonstrates a central keratin plug.


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This lesion, which is located at the outer edge of the vermilion border of the lip, demonstrates a prominent core or plug of keratin.


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  1. Appearance on initial presentation. Note small, central keratin-filled invagination.
  2. Same lesion 1 week later showing slight enlargement.
  3. Same lesion showing further growth 3 weeks after initial presentation.


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Low-power microscopic view showing extensive epidermal proliferation with a central keratin plug. Note the characteristic acute angle (or “buttress”) formed between the overlying epithelium and the lesion.



What two rare, heritable conditions are associated with early onset of multiple keratoacanthomas?

  1. Ferguson-Smith syndrome
  2. Witten-Zak syndrome


What condition associated with internal malignancy manifests later in life as numerous papules of the skin and upper digestive tract?

Grzybowski syndrome


What is the treatment and prognosis for keratoacanthoma?

  • many authorities advocate excision due to similarity to SCC
  • conventional surgical excision is preferred
  • approximately 4% to 8% recur
  • malignant transformation has been reported


What is the most common cause (more than 90%) of oral malignancies?

squamous cell carcinoma


The cause of oral squamous cell carcinoma is multifactorial. What are nine factors associated with development of oral squamous cell carcinoma?

  1. tobacco use
  2. betel quid
  3. alcohol
  4. occupational or environmental exposures
  5. radiation
  6. dietary factors
  7. bacterial, fungal, or viral infections
  8. immunosupression
  9. mutations or epigenetic changes


Clinical Features

  • most often occurs in older men
  • patients often aware of alteration for 4 to 8 months
  • minimal pain during early growth phase
  • variable presentation
    • fungating, papillary, and verruciform (exophytic)
    • invasive, burrowing, and ulcerated (endophytic)
    • white patch (leukoplakic)
    • red patch (erythroplakic)
    • red-and-white patch (erythroleukoplakic)
  • can cause bone destruction ("moth-eaten" radiolucency)
  • most occur on lip, tongue, and floor of mouth

Histopathological Features

  • invasive islands and cords of malignant squamous epithelial cells
  • may breach perineurium (perineural invasion)
  • may invade lumina of veins or lymphatics (vascular invasion)
  • may induce dense fibrosis (desmoplasia or scirrhous change)
  • may cause formation of new blood vessels (angiogenesis)
  • abundant eosinophilic cytoplasm
  • darkly staining (hyperchromatic) nuclei
  • increased nuclear-to-cytoplasmic ratio
  • variable cellular and nuclear pleomorphism
  • foci of concentrically layered, keratinized cells ("keratin pearls")

squamous cell carcinoma

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Leukoplakic lesion with a granular surface on the left ventrolateral tongue.

squamous cell carcinoma

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Speckled erythroplakia of the left posterior buccal mucosa.

squamous cell carcinoma

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An exophytic lesion of the posterior lateral tongue demonstrates surface nodularity and minimal surface keratin production. It is painless and indurated.

squamous cell carcinoma

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An exophytic buccal lesion shows a roughened and irregular surface with areas of erythema admixed with small areas of white keratosis.

squamous cell carcinoma

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Chronic ulcerated lesion on the right ventral surface of the tongue. The rolled anterior margin felt indurated on palpation.

squamous cell carcinoma

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An ulcerated lesion of the hard palate demonstrates rolled borders and a necrotic ulcer bed. It was painless, although it had partially destroyed underlying palatal bone, resulting in a "moth-eaten" radiolucency.

squamous cell carcinoma

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Bone involvement is characterized by an irregular, “moth-eaten” radiolucency with ragged margins—an appearance similar to that of osteomyelitis.

squamous cell carcinoma

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Crusted, ulcerated nodule of the lower lip vermilion. Risk factors in this patient included chronic sun exposure as well as immunosuppression due to bone marrow transplantation.

squamous cell carcinoma

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Ulcerated mass of the lower lip vermilion. The tumor usually grows slowly, and most patients are aware of a “problem” in the area for 12 to 16 months before diagnosis.

squamous cell carcinoma

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Patient neglect can result in extensive involvement, even in a readily visible site such as the lip vermilion. This ulcerating lesion of the lower lip had been present for more than 1 year before diagnosis.

squamous cell carcinoma

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Diffuse, red and white lesion of the posterior lateral border of the tongue.

squamous cell carcinoma

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Granular red and white lesion in the anterior floor of mouth.

squamous cell carcinoma

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Red and white granular lesion of the posterior lingual mandibular gingiva.

squamous cell carcinoma

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An innocuous, pebbled surface change of the gingiva was interpreted as inflammatory until multifocal white keratoses developed.

squamous cell carcinoma

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An exophytic lesion with an irregular and pebbled surface. There is a linear indentation along the facial aspect resulting from pressure from the patient's lower denture. The underlying alveolar bone was destroyed.

squamous cell carcinoma

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  1. Large, erythroplakic lesion involving the left soft palate and tonsillar region.
  2. Immunohistochemical staining showed the tumor to be positive for p16.
  3. In situ hybridization demonstrated presence of intranuclear HPV 16 DNA.

oropharyngeal squamous cell carcinoma

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Metastasis of oral squamous cell carcinoma occurs largely via the lymphatics to the ipsilateral cervical lymph nodes. What are three clinical signs of a cervical lymph node that contains metastatic carcinoma?

  1. firm
  2. nontender
  3. enlarged


Extracapsular spread is a microscopic feature associated with poor prognosis. What clinical sign indicates that the malignant cells have perforated the capsule of the node and invaded into surrounding tissues?

it will feel “fixed”

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Firm, painless enlargements as seen in this patient with a posterior lateral tongue carcinoma.

lymph node metastasis, squamous cell carcinoma


What are the three most common sites for distant metastasis of squamous cell carcinoma?

lungs, liver, and bones


Carcinoma of the lower lip and oral floor usually spreads to which lymph nodes?



Carcinoma of the posterior portions of the mouth usually spreads to which lymph nodes?

superior jugular and digastric


Carcinoma of the oropharynx usually spreads to which lymph nodes?

jugulodigastric or retropharyngeal


Tumor size and the extent of metastatic spread are the best prognostic indicators for oral squamous cell carcinoma. What is the process of quantifying these called?



Staging is the process of quantifying tumor size and the extent of metastatic spread. What are the three parameters of staging?

  1. T—size of the primary tumor
  2. N—regional lymph node involvement
  3. M—distant metastasis

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  1. Tumor has breached the perineurium encasing this nerve fiber.
  2. Tumor is present within the lumen of this vessel.

squamous cell carcinoma

  1. perineural invasion
  2. angioinvasion


What process accesses the degree of resemblance of squamous cell carcinoma to normal squamous epithelium and the amount of keratin production?



Lesions are graded on a three-point (grades I to III) or a four-point (grades I to IV) scale. What do these numerals indicate?

The higher the numeral, the less differentiated the tumor.

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  1. Low-power photomicrograph showing islands of malignant squamous epithelium invading into the lamina propria.
  2. High-power view showing dysplastic epithelial cells with keratin pearl formation.

squamous cell carcinoma, well-differentiated (grade I)

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The numerous pleomorphic cells within the lamina propria represent anaplastic carcinoma.

squamous cell carcinoma, poorly-differentiated (grade III/IV)

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Although no keratinization is seen in this medium-power view, these malignant cells are still easily recognizable as being of squamous epithelial origin.

squamous cell carcinoma, moderately-differentiated (grade II/III)


What is the treatment and prognosis for squamous cell carcinoma?

  • clinical staging guides treatment
  • most lip vermilion carcinomas are treated by surgical excision
  • advanced cases may be treated by radiation or chemoradiation
  • early intraoral lesions usually are treated with surgery
  • moderate cases treated with surgery and radiation or chemoradiation
  • advances cases treated with radiation or chemoradiation
  • possible nodal involvement may indicate neck dissection or biopsy
  • 5-year relative survival rate is approximately 64% combined
  • stage is the best prognostic indicator for intraoral and lip carcinomas
  • HPV status the best prognostic indicator for oropharyngeal carcinoma


Neck dissection may be indicated for cases of clinically evident or suspected cervical lymph node metastasis. What are the three types of neck dissection?

  1. radical neck dissection (removal of all structures in the lateral triangle)
  2. modified radical neck dissection (removal of only lymphatic structures)
  3. selective neck dissection (removal of only select node groups)


The first lymph node in the lymphatic basin to receive drainage from the tumor.

sentinel lymph node


Clinical Features

  • low-grade variant of oral squamous cell carcinoma
  • predominantly in older men (65 to 70 years)
  • occurs on vestibule, buccal mucosa, gingiva, tongue, hard palate
  • location corresponds to site of tobacco placement
  • usually extensive by time of diagnosis
  • diffuse, well-demarcated, painless, thick plaque
  • papillary or verruciform surface projections
  • typically white, but may be erythematous or pink

Histopathological Features

  • wide, elongated rete ridges “pushing” into underlying connective tissue
  • papillary or verruciform surface
  • parakeratin-filled clefts between surface projections
  • intense inflammatory cell infiltrate

verrucous carcinoma

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Extensive papillary, white lesion of the maxillary vestibule. The involved area often corresponds to the site of chronic tobacco placement.

verrucous carcinoma

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Large, exophytic, papillary mass of the maxillary alveolar ridge. It is not unusual for a tumor to be present for 2 to 3 years before definitive diagnosis.

verrucous carcinoma

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  1. Low-power photomicrograph showing marked epithelial hyperplasia with a rough, papillary surface and keratin plugging (parakeratin clefts).
  2. High-power view showing bulbous rete ridges without significant dysplasia.

verrucous carcinoma


What is the treatment and prognosis for verrucous carcinoma?

  • surgical excision
  • selective neck dissection for cervical lymph node enlargement
  • 90% of patients are disease free 5 years after surgery
  • radiotherapy is an alternative, but provides poorer local control


Clinical Features

  • rare variant of squamous cell carcinoma
  • may develop after more differentiated SCC ("dedifferentiation")
  • may arise anywhere within the upper aerodigestive tract
  • predilection for the larynx and oral cavity
  • common on alveolar mucosa, tongue, buccal mucosa, lower lip
  • males are affected more often; mean age is 57 years
  • typically a pedunculated, polypoid mass with ulcerated suface
  • pain and paresthesia are prominent features
  • grows rapidly and metastasizes early

Histopathological Features

  • fascicles of anaplastic, spindle-shaped cells
  • numerous mitotic figures

spindle cell carcinoma

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Large polypoid mass arising from the right lateral tongue. Pain and paresthesia are prominent features of this particular lesion.

spindle cell carcinoma

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Streaming fascicles of pleomorphic spindle cells that represent anaplastic epithelial cells. Numerous mitotic figures often are present.

spindle cell carcinoma


What is the treatment and prognosis for spindle cell carcinoma?

  • radical surgery
  • neck dissection when clinically positive nodes are present
  • 5-year disease-free survival rate is approximately 30%
  • most deaths occur within 1 year of diagnosis


Clinical Features

  • rare squamous cell carcinoma variant
  • may involve tongue, oral floor, and mucosal surfaces
  • usually in older adults with a male predilection
  • nodular, broad-based, variably painful mass
  • most have cervical lymph node metastasis at diagnosis

Histopathological Features

  • surface squamous cell carcinoma and underlying adenocarcinoma
  • glandular component most prominent in deeper portions
  • mucicarmine staining demonstrates intracytoplasmic mucin

adenosquamous carcinoma


What is the treatment and prognosis for adenosquamous carcinoma?

  • radical surgical excision
  • possibly adjuvant radiation or chemoradiation therapy
  • poor prognosis; 5-year survival rate is approximately 13%


Clinical Features

  • squamous cell carcinoma variant
  • arises primarily in the upper aerodigestive tract
  • predilection for larynx, hypopharynx, and tongue base
  • occurs in persons 40 to 85 years of age
  • arises more commonly in males than females
  • fungating mass or ulcer
  • may be painful or interfere with swallowing

Histopathological Features

  • superficial squamous cell carcinoma
  • deeper invasive basaloid epithelium
  • distinct interface between the two components
  • tumor islands often are surrounded by mucoid stroma

basaloid squamous carcinoma

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Sheets of basaloid squamous epithelium exhibiting a high mitotic index and tumor necrosis. These lesions consist of a superficial squamous cell carcinoma and deeper invasive basaloid epithelium.

basaloid squamous carcinoma


What is the treatment and prognosis for basaloid squamous carcinoma?

  • surgery, often followed by radiation or chemoradiation therapy
  • considered a highly aggressive malignancy
  • mean survival of only 23 months
  • significantly improved survival among HPV-positive cases


Clinical Features

  • relationship to occupational wood and leather dust exposure
  • mainly affects older adults
  • slight male predilection
  • chronic unilateral nasal stuffiness
  • mass or ulceration of the hard palate
  • radiographs often reveal a “moth-eaten” bone destruction
  • panoramic radiograph shows a cloudy sinus

Histopathological Features

  • the majority represent squamous cell carcinomas

carcinoma of the maxillary sinus

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The tumor has produced a bulge of the posterior maxillary alveolar ridge and is beginning to ulcerate through the surface mucosa. A panoramic radiograph shows a cloudy sinus with destruction of its bony wall.

carcinoma of the maxillary sinus


What is the treatment and prognosis for carcinoma of the maxillary sinus?

  • if confined to maxillary sinus, treated by hemimaxillectomy
  • if perforated, treated by surgery with radiotherapy or chemotherapy
  • poor prognosis; 5-year survival rate of approximately 40%


Clinical Features

  • occurs over a broad age range (third through ninth decades)
  • more common in males (2 : 1 to 3 : 1)
  • rapid development of locally extensive disease
  • large mass involving multiple regions of sinonasal tract
  • rapid onset of sinonasal symptoms (e.g. obstruction, discharge)
  • imaging reveals a large, expansile sinonasal mass

Histopathological Features

  • trabeculae, ribbons, sheets, and nests of polygonal cells
  • minimal cytoplasm and pleomorphic nuclei
  • numerous mitotic figures
  • prominent necrosis, apoptosis, and lymphovascular invasion

sinonasal undifferentiated carcinoma (SNUC)

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T1-weighted magnetic resonance image (MRI) showing a large destructive mass filling the right maxillary sinus with extension into the orbital region and nasal cavity.

sinonasal undifferentiated carcinoma (SNUC)


What is the treatment and prognosis for sinonasal undifferentiated carcinoma (SNUC)?

  • aggressive multimodal therapy
  • surgical resection with adjuvant radiation and/or chemotherapy
  • unresectable disease treated by definitive chemoradiation therapy
  • 5-year survival rates range from 20% to 74%
  • local recurrence is common
  • metastasis is usually to cervical lymph nodes, bone, liver, or brain


Clinical Features

  • most commonly affects those 40 to 60 years old
  • three times more common in men than in women
  • usually arises from lateral nasopharyngeal wall
  • first sign is usually cervical lymph node metastasis
  • epistaxis, nasal obstruction, and pharyngeal pain

Histopathological Features

  • identical to squamous cell carcinoma (keratinizing squamous cell type)
  • round cells that produce no keratin (differentiated nonkeratinizing type)
  • undifferentiated cells (undifferentiated nonkeratinizing type)

nasopharyngeal carcinoma

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This patient initially appeared with metastatic carcinoma in the left lateral neck. Further evaluation revealed a primary tumor of the nasopharynx.

nasopharyngeal carcinoma

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Poorly differentiated tumor exhibiting sheets of rounded tumor cells. The lesions arise from the lining epithelium of the lymphoid tissue–rich nasopharynx.

nasopharyngeal carcinoma


What is the treatment and prognosis for nasopharyngeal carcinoma?

  • radiotherapy is the mainstay for early-stage disease
  • advanced disease requires chemotherapy and radiation therapy
  • for all stages combined, the relative 5-year survival rate is 59%


What is the most common of all cancers?

basal cell carcinoma


Clinical Features

  • found on the skin of the head and neck (80%)
  • results from cumulative UV radiation exposure
  • dysregulation of the hedgehog signaling pathway
  • most often affects fair-complexioned white adults
  • most patients are older than 40 years at diagnosis
  • males are affected about twice as often as females
  • firm, painless, slowly-enlarging papule
  • develops a central depression or umbilication
  • telangiectatic blood vessels usually are evident
  • pearly opalescent quality when pressed

Histopathological Features

  • uniform, ovoid, dark-staining basaloid cells
  • medium-sized nuclei and little cytoplasm
  • well-demarcated islands and strands
  • islands demonstrateing peripheral palisading
  • actinic damage in the form of solar elastosis

basal cell carcinoma

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Early noduloulcerative lesion of the forehead showing raised, rolled borders and focal ulceration. Fine, telangiectatic blood vessels can be seen on the surface.

basal cell carcinoma

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Noduloulcerative lesion of the upper lip demonstrating telangiectasia and small ulceration. When the lesion is pressed, a pearly opalescent quality is discerned.

basal cell carcinoma

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This tumor was neglected for many years and became exceptionally large. Untreated lesions of this type continue to enlarge slowly, with ulceration and destruction of underlying structures—hence the term "rodent ulcer".

basal cell carcinoma

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Pigmented lesion of the cheek. Usually the pigment is not distributed uniformly, as it would be in a melanocytic nevus.

basal cell carcinoma

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Low-power photomicrograph showing ulceration of the epidermal surface associated with an invading tumor of hyperchromatic epithelial cells. Inset demonstrates islands of basophilic epithelium with peripheral palisading.

basal cell carcinoma


What are seven features associated with increased risk for recurrence among cutaneous basal cell carcinomas of the head and neck?

  1. lesions of 6 mm or more in the “mask area”
  2. lesions more than 1 cm outside “mask area”
  3. ill-defined clinical borders
  4. micronodular, infiltrative, and sclerosing types
  5. perineural invasion
  6. recurrent lesions
  7. lesions arising in immunosuppressed individuals


What is the treatment and prognosis for basal cell carcinoma?

  • surgical excision for lesions with low risk of recurrence
  • high risk lesions treated by Mohs micrographic surgery
  • alternative treatments (e.g. topicals) may be effective for low-risk
  • recurrence is uncommon
  • metastasis is exceptionally rare


This technique uses intraoperative, frozen-section evaluation of specially mapped and marked surgical specimens to ensure complete tumor removal.

Mohs micrographic surgery


Clinical Features

  • aggressive malignancy with neuroendocrine features
  • occurs on the skin of the head and neck region
  • UV light exposure and old age are major risk factors
  • increased among immunocompromised individuals
  • mostly affects individuals 70 years or older (70%)
  • mainly affects whites (95%)
  • exhibits a male predominance
  • occurs primarily on sun-exposed areas
  • rapidly enlarging, smooth, dome-shaped nodule
  • asymptomatic
  • prominent surface vessels (telangiectasias)

Histopathological Features

  • sheets and strands of round, basophilic cells
  • infiltration into dermis and subcutaneous fat
  • pseudoglandular, trabecular, cribriform (“Swiss cheese”) patterns
  • overlapping nuclei, finely granular chromatin, scant cytoplasm
  • indistinct cell borders, and brisk mitotic activity

Merkel cell carcinoma

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Red nodule on the vermilion border of the upper lip. It is asymptomatic and expanding rapidly. These are often found in immunosupressed patients, older patients, and on the sun-exposed skin of fair-complexioned individuals.

Merkel cell carcinoma

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A sheet of undifferentiated basophilic cells is seen beneath the epidermal surface. These will be seen infiltrating into dermis and subcutaneous fat.

Merkel cell carcinoma


Some authors have used the acronym AEIOU to summarize the salient clinical findings of Merkel cell carcinoma. What does this stand for?

  1. asymptomatic
  2. expanding rapidly
  3. immunosuppression
  4. old age
  5. ultraviolet-exposed fair skin


What is the treatment and porgnosis for Merkel cell carcinoma?

  • surgery (i.e., wide local excision or Mohs micrographic surgery)
  • often is combined with adjuvant radiotherapy
  • chemotherapy is reserved for cases with distant metastasis
  • recurrence in 55% of cases (often in draining lymph nodes)
  • approximately 25% develop additional malignancies


Clinical Features

  • UV radiation exposure is a major etiologic factor
  • acute UV exposure may be more important than chronic
  • mucosal type is much more aggressive than cutaneous
  • most commonly develop in white adults
  • most cases arise in individuals 45 through 84 years
  • female predilection under 40 years, male later in life
  • four clinicopathologic types
  • two patterns of growth: 1) radial phase and 2) vertical phase

Histopathological Features

  • atypical, enlarged melanocytes
  • nuclear pleomorphism and hyperchromatism
  • spread of lesional cells along basal layer (radial phase)
  • malignant melanocytes invading connective tissue (vertical phase)



Clinical Features

  • most common form of cutaneous melanoma (70%)
  • interscapular area of males, back of legs of females
  • macule or plaque with a variety of potential colors
  • most smaller than 3 cm in diameter at diagnosis

superficial spreading melanoma

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This lesion on the neck demonstrates ABCDE warning signs: asymmetry, border irregularity, color variegation, diameter larger than a pencil eraser, and evolving larger size.

superficial spreading melanoma


Clinical Features

  • represents 15% of cutaneous melanomas
  • one-third develop in the head and neck
  • thought to begin in the vertical growth phase
  • nodular elevation that rapidly invades connective tissue

nodular melanoma


Clinical Features

  • accounts for 5% to 10% of cutaneous melanomas
  • develops from precursor ("Hutchinson freckle")
  • almost exclusive to sun-exposed skin
  • affects fair-complexioned older adults
  • large, slowly expanding macule
  • irregular borders and a variety of colors

lentigo maligna melanoma

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A slowly evolving pigmented lesion of the facial skin in an older adult man. This lesion is thought to begin almost immediately in the vertical growth phase.

lentigo maligna melanoma


Clinical Features

  • most common form of melanoma in blacks
  • most common form of oral melanoma
  • on palms, soles, and mucous membranes
  • dark, irregularly marginated macule
  • develops a nodular invasive growth phase

acral lentiginous melanoma

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This discrete area of pigmentation, measuring approximately 5 mm in diameter, was discovered on the posterior hard palate of a middle-aged woman during a routine oral examination.

oral melanoma

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Diffuse, splotchy area of pigmentation of the lateral hard palate. Approximately 70% to 80% of these lesions are found on the hard palate or maxillary alveolus.

oral melanoma

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Extensive, pigmented mass of the palate and maxillary alveolar ridge. An exophytic component is evident, indicating that the lesion is in the vertical growth phase.

oral melanoma

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The radial growth phase is characterized by the spread of atypical melanocytes along the basilar portion of the epidermis. Also note the presence of individual melanocytes invading the higher levels of the epithelium.

superficial spreading melanoma

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This palatal melanoma demonstrates numerous atypical melanocytes in the basilar portion of the epithelium with invasion into the superficial lamina propria.

acral lentiginous melanoma

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  1. Low-power photomicrograph showing a nodular mass of malignant melanocytes invading into the dermis. Note the lack of radial growth in the adjacent overlying epidermis.
  2. Higher-power photomicrograph showing atypical spindle-shaped melanocytes.

nodular melanoma


Because many clinical similarities exist between cutaneous melanoma and melanocytic nevus, an “ABCDE” clinical evaluation system has been developed to help distinguish between these two entities. What does this stand for?

  1. asymmetry (uncontrolled growth)
  2. border irregularity (often with notching)
  3. color (brown, black, white, red, blue)
  4. diameter over 6 mm (pencil eraser)
  5. evolving (shape, surface, symptoms)


Depth of invasion is an important prognostic factor for cutaneous melanoma. What is Clark's classification for cutaneous melanoma?

  1. level I—cells confined to epithelium
  2. level II—cells penetrating papillary dermis
  3. level III—cells filling papillary dermis
  4. level IV—cells extend into reticular dermis
  5. level V—cells invading subcutaneous fat


What is the treatment and prognosis for melanoma?

  • surgical excision is the mainstay
  • lymph node dissection if clinically evident regional metastasis
  • most early-stage lesions cured by surgery alone
  • adjuvant radiation or immunotherapy if high risk for recurrence
  • 5-year survival rates exceed 90% when confined to the skin
  • 5-year survival rates of 40% to 78% for regional metastasis
  • 5-year survival rates of 15 to 20% for distant metastasis
  • progosis is worse for head/neck than extremities
  • prognosis for oral melanoma is extremely poor
  • 5-year survival rates in the range of only 10% to 25%