Oral and Maxillofacial Pathology: Chapter 10: Epithelial Pathology Flashcards

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?

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?

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

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

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

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

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.

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

What are koilocytes?

What is the treatment and prognosis for squamous papilloma?

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

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

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

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

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.

What is the treatment and prognosis for verruca vulgaris?

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

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

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

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

What is the treatment and prognosis for condyloma acuminatum?

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)

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

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

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

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

What is the treatment and prognosis for multifocal epithelial hyperplasia?

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

Erythematous, papillary growth on the nasal septum.

What is the treatment and prognosis for fungiform papilloma?

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

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

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

What is the treatment and prognosis for inverted papilloma?

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

What is the treatment and prognosis for cylindrical cell papilloma?

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

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

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

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

What is the treatment and prognosis for molluscum contagiosum?

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

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

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.

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).

What is the treatment and prognosis for verruciform xanthoma?

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")

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

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

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

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

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

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

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

What is the treatment and prognosis for seborrheic keratosis?

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

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

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

What is the treatment and prognosis for sebaceous hyperplasia?

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

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?

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

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

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

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

What is the treatment and prognosis for actinic lentigo?

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)

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

What is the treatment and prognosis for lentigo simplex?

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

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?

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

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

A well-demarcated brown macule of the gingival mucosa.

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.

What is the treament and prognosis for oral melanotic macule?

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

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.

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

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

What is the treatment and prognosis for oral melanoacanthoma?

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)

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

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

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

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

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

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.

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

What is the treatment and prognosis for melanocytic nevus?

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

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

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

What is the treatment and prognosis for congenital melanocytic nevus?

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

Elevated brown lesion of the skin showing surrounding depigmentation.

What is the treatment and prognosis for halo nevus?

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

What is the treatment and prognosis for Spitz nevus?

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

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

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.

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

What is the treatment and prognosis for blue nevus?

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.

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.

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

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

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.

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?

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

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.

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

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

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.

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.

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

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

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.

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.

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

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?

What type of kerotosis is shown in this figure?

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)

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

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

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

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

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

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

What is the treatment and prognosis for leukoplakia?

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

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

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

What is the treatment and prognosis for erythroplakia?

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

Extensive recession of the anterior mandibular facial gingiva.

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.

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

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

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.

What is the treatment and prognosis for tobacco pouch keratosis?

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.

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

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

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

What is the treatment and prognosis for oral submucous fibrosis?

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

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.

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.

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

What is the treatment and prognosis of nicotine stomatitis?

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)

What is solar elastosis?

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

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.

What is the treatment and prognosis of actinic keratosis?

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)

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

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

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

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

What is the treatment and prognosis for actinic cheilosis?

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

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

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

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.

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?

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

What is the treatment and prognosis for keratoacanthoma?

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

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

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")

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

Speckled erythroplakia of the left posterior buccal mucosa.

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

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

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

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.

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

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.

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.

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.

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

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

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

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

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.

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.

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?

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?

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

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

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?

Carcinoma of the oropharynx usually spreads to which lymph nodes?

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

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?

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.

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

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

What is the treatment and prognosis for squamous cell 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?

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

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

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

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.

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.

What is the treatment and prognosis for verrucous carcinoma?

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

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

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

What is the treatment and prognosis for spindle cell carcinoma?

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

What is the treatment and prognosis for adenosquamous carcinoma?

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

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.

What is the treatment and prognosis for basaloid squamous carcinoma?

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

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.

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

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

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.

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

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)

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

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

What is the treatment and prognosis for nasopharyngeal carcinoma?

What is the most common of all cancers?

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

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

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

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".

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

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.

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

What is the treatment and prognosis for basal cell carcinoma?

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

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

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.

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

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

What is the treatment and porgnosis for Merkel cell carcinoma?

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

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

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

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

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.

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

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.

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.

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.

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.

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

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.

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?

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

What is the treatment and prognosis for melanoma?