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HEENT - Skin Pathology

Terms in this set (92)

Acute Inflammatory Dermatoses
Urticaria (Hives / Wheals)

Acute Eczematous Dermatitis

Erythema Muliforme
Urticaria (Hives/ Wheals) - Pathogenesis
D/t Type 1 hypersensitivity reaction -antigens trigger mast cell degranulation by binding to immunoglobulin E (IgE) antibodies attached to the mast cell surface through their Fc receptor.

Leads to localized mast cell degranulation, microvascular hyperpermeability

Antigen induced (pollens, foods, drugs, insect bite, antibiotics). In majority, no clinical cause is discovered.
Urticaria (Hives/ Wheals) - Morphology
Intensely pruritic, erythematous, raised wheals like rash.

It is usually a self-limiting
Urticaria (Hives/ Wheals) - Clinical Features
20-40 yo

Lifetime prevalence of approx. 20% in general population

Diagnosis is clinical

Sharply demarcated, pruritic edematous plaques

Develop and fade within 24 hours

Type I hypersensitivity reaction
Urticaria (Hives/ Wheals) - Tx
Avoidance of triggers. First-line therapy - antihistamines (histamine H1 blockers).

Leukotriene receptor antagonists, and brief corticosteroid bursts may be used.

More than one-half of patients - improvement of symptoms within one year.
Acute Eczematous Dermatitis - Pathogenesis
T-cell-mediated type IV hypersensitivity reaction

Many entities - indistinguishable histologically

Allergic contact dermatitis is triggered by exposure to an environmental contact-sensitizing agent, such as poison ivy, that chemically reacts with self-proteins, creating neoantigens that can be recognized by the T cell arm of the adaptive immune system.
Acute Eczematous Dermatitis - Morphology
Lesions of acute eczematous dermatitis are pruritic, edematous, oozing plaques, often containing vesicles and bullae. -With persistent antigen exposure, lesions may become scaly (hyperkeratotic) as the epidermis thickens (acanthosis)

Some changes are produced or exacerbated by scratching of the lesion

Causes skin dryness, redness, crusting, cracking, blistering, oozing, or thickening of the skin.

Areas involved - wrists, ankles, shins, forearms, neck, and behind the knees.
Acute Eczematous Dermatitis - Clinical Features
Very common skin condition that affects children and adults.

Patients may have a history of asthma or hay fever.
Acute Eczematous Dermatitis - Types
Allergic Contact Dermatitis

Atopic Dermatitis

Drug-Related Eczematous Dermatitis
Allergic Contact Dermatitis
Cosmetic, fragrances, poison ivy, latex, nickel allergy, rubber

Stems from topical exposure to an allergen and is caused by delayed
Atopic Dermatitis
Formerly attributed to allergen exposure, now thought to often stem from defects in keratinocyte barrier function, defined as skin with increased permeability to substances to which it is exposed, such as potential antigens
Drug-Related Eczematous Dermatitis
Hypersensitivity reaction to a drug
Erythema Multiforme - Pathogenesis
Uncommon self-limited hypersensitivity reaction to certain infections and drugs mediated by CD8+ cytotoxic T lymphocytes. It affects individuals of any age and is associated with the following conditions:

Herpes simplex virus and Mycoplasma pneumoniae,erythema multiforme, also SLE
*drugs (sulfonamides, penicillin, barbiturates, salicylates) and infections
Erythema Multiforme - Morphology
Target like, the erythema multiforme lesions can be isolated, recurrent, or persistent

Severe form (SJS and TEN)
Erythema Multiforme - Clinical Features
Symmetric on the extremities (especially on extensor surfaces)

Spread centripetally

"Multiforme" lesions-macules, papules, vesicles, bullae, and target-like lesions
Erythema Multiforme - Key Identification
Targetoid lesions

Etiology - self-limited hypersensitivity reaction to certain infections and drugs
Chronic Inflammatory Dermatoses
Psoriasis
Lichen Plamus
Lichen Simplex Chronicus
Psoriasis - Pathogenesis
T cell-mediated inflammatory disease, presumed to be autoimmune in origin.

Both genetic and environmental factors contribute to the risk.
Psoriasis - Morphology
Psoriasis - Clinical Features
Common -- 1-2% of population

Elbows, scalp, intergluteal cleft and glans penis
30% cases - nail involvement
15% - associated arthritis - correlates with severity
Psoriasis - Key Features
Pink-salmon color plaques covered by adherent silver-white scale

Koebner Phenomenon

Auspitz Sign
Koebner Phenomenon
Lesions induced by local trauma
Auspitz Sign
Minute bleeding points when scale is lifted from plaque
Psoriasis - Tx
Corticosteroids, vitamin D analogs, tazarotene, phototherapy, biologic therapies

Mild: ointment containing corticosteroids or other immunomodulatory agents

Severe: phototherapy (which has immunosuppressive effects) or systemic therapy with immunosuppressive agents such as methotrexate or Biologics (TNF antagonists, Humira)
Lichen Planus - Morphology
Wickham striae

Saw tooth acanthosis, band-like superficial lymphoid infiltrate
Lichen Planus - Clinical Features
Uncommon

Middle age adults

Cutaneous lesions are multiple and symmetrically distributed

Extremities, wrists, elbows and on the vulva and glans penis.

70% involve the oral mucosa (white papules with netlike appearance)
Lichen Planus - Tx
Resolve spontaneously within 1 to 2 years, but the oral lesions may persist and be of sufficient severity to interfere with food intake.

Usually self-limited

Mucous membranes may be more persistent and resistant to treatment.
Lichen Planus - Key Features
5P's: "Pruritic, purple, polygonal, planar papules, and plaques"

Antihistamines, topical or oral or injectable corticosteroid (1st line is topical) , PUVA therapy, retinoic acid, immunosuppressants (systemic)
Lichen Simplex Chronicus - Pathogenesis
Manifests as roughening of the skin

Response to local repetitive trauma, usually from rubbing or scratching.

Nodular forms exist that are referred to as prurigo nodularis.

Pathogenesis of lichen simplex chronicus is not understood, but the trauma probably induces epithelial hyperplasia and eventual dermal scarring.
Lichen Simplex Chronicus - Morphology
At least 10x thicker than normal epidermis
Lichen Simplex Chronicus - Clinical Features
The lesions often are raised, erythematous, and scaly and can be mistaken for keratinocytic neoplasms. Lichen simplex chronicus can be superimposed on and mask another (often pruritic) dermatosis.
Infectious Dermatoses
Bacterial Infection (Impetigo)
Fungal Infection - Tinea
Verrucae (Warts)
Bacterial Infection (Impetigo) - Pathogenesis
Superficial bacterial infection of skin of face and hand, bacteria produce toxin

Spread by direct contact
Bacterial Infection (Impetigo) - Morphology
Results in superficial blister

Special stain highlights bacteria

"Honey-colored crust"
Bacterial Infection (Impetigo) - Clinical Features
Staph aureus (most common) or group A streptococci
Bacterial Infection (Impetigo) - Tx
Topical antibiotics such as mupirocin, retapamulin, and fusidic acid.

Oral antibiotic therapy can be used for impetigo with large bullae or when topical therapy is impractical.
Fungal Infection -
Tinea - Pathogenesis
Tinea is the name of a group of diseases caused by a fungus, not serious, but they can be uncomfortable.

Caused by dermatophytes and are classified by the involved site.

The most common infections in prepubertal children are tinea corporis and tinea capitis, whereas adolescents and adults are more likely to develop tinea cruris, tinea pedis, and tinea unguium (onychomycosis).
Fungal Infection -
Tinea - Morphology
Clinical diagnosis can be unreliable (mimics)

Tinea corporis can be confused with eczema, tinea capitis can be confused with alopecia areata, and onychomycosis can be confused with dystrophic toe-nails from repeated low-level trauma.

Confirm suspected onychomycosis and tinea capitis with a potassium hydroxide preparation or culture.
Fungal Infection -
Tinea - Tx
Respond to topical antifungal agents - terbinafine cream or butenafine cream

Oral antifungal agents- extensive disease
Tinea capitus
scalp, children
Tinea corporis
all ages and areas
Tinea cruris
inguinal area during warm weather
Tinea pedis
athletes foot
Tinea barbae
adult men
Nail infection
onychomycosis
Verrucae (Warts) - Pathogenesis
HPV DNA virus (cause)

Direct transmission or autoinoculation

Types:
-verruca vulgaris--common wart
-verruca plana--flat wart
-verruca plantaris--soles of feet
-condyloma acuminatum- anogenital warts (HPV 6, 11)
Verruca Vulgaris
Self-limited

Regressing spontaneously within 6 months to 2 years

Multiple papules with rough pebble-like surfaces
Verrucae (Warts) - Tx
Dx = Viral typing by ISH and PCR, biopsy usually

Local destruction (acids, cryotherapy, electrodesiccation-curettage), chemotherapy, or immunotherapy
-Choice of treatment varies with the age and wishes of the patient, the potential side effects of the treatment, and the location of the lesions
Molluscum Contagiosum
Trunk and anogenital area

Small raised lesions with dimple in center
-Umbilicated papule and nodules
-Molluscum contagiosum is a common, self-limited viral disease of the skin caused by a DNA poxvirus.
-Common, direct contact--children & young adults
-if genital molluscum, could be a sign of abuse
Primary Blistering Diseases
Most are autoimmune diseases with antibodies directed against cell adhesion molecules

Classified by:
• Level of epidermal separation - intraepidermal vs subepidermal
• Nature of associated inflammation - eosinophils vs neutrophils
Blistering (Bullous) Disorders
Pemphigus (Vulgaris)
Bullous Pemphigoid
Dermatitis Herpetiformis
Pemphigus (Vulgaris) - Pathogenesis
Intraepidermal blistering disorder associated with IgG autoantibodies to intercellular adhesion molecules desmogleins causing acantholysis (breakdown of bonds between keratinocytes)

Antibodies to desmoglein:
1.Pemphigus vulgaris
-Suprabasilar blister, anti-Dsg1 & anti-Dsg3
2.Pemphigus foliaceus
-Subcorneal blister, anti-Dsg1
-Endemic in Brazil (fogo selvagem)
-A rare, milder form of pemphigus
3.Paraneoplastic pemphigus
Pemphigus (Vulgaris) - Morphology
Lesions are superficial flaccid vesicles and bullae that rupture easily, leaving deep and often extensive erosions covered with a serum crust
Pemphigus (Vulgaris) - Clinical Feautres
Direct IF for IgG - Fishnet-like pattern of IgG deposits between keratinocytes (intercellular pattern)
Pemphigus (Vulgaris) - Key Features
Most common type (but still rare)

Axilla, groin, trunk, points of pressure

Suprabasilar acantholysis leading to intraepidermal blister
Bullous Pemphigoid - Pathogenesis
Subepidermal non-acantholytic blister; tense and not easily ruptured

Linear anti-IgG along the DE junction. Autoantibodies against hemidesmosomes - Anti BPAG2 - are cause of blisters

*hemidesmosomes
Bullous Pemphigoid - Morphology
Large tense bullae
Bullous Pemphigoid - Tx
Systemic prednisone, alone or in combination with agent such as azathioprine

Mild cases may require only topical corticosteroids. -Methotrexate may be used in patients with severe disease who are unable to tolerate prednisone.

A self-limiting disease, but may last from months to years. It is rarely fatal, and carries a good prognosis.
Bullous Pemphigoid - Key Features
Elderly individuals

Sites of involvement include the inner aspects of the thighs, flexor surfaces of the forearms, axillae, groin, and lower abdomen.

Oral lesions are present in 10% to 15% of affected individuals, usually appearing after the cutaneous lesions.
Dermatitis Herpetiformis - Pathogenesis
Small subepidermal collections of neutrophils in papillary dermis

Strong association with Celiac disease (responds to gluten-free diet)

Dermatitis herpetiformis IF IgA granular deposits at the tips of dermal papillae

Typically on knees and elbows
Dermatitis Herpetiformis - Morphology
Plaques and vesicles are extremely pruritic.

Abscess= neutrophils collect in tissue (micro-abscess)
Dermatitis Herpetiformis - Clinical Features
The disease affects predominantly males, most often in the third and fourth decades of life.

In some cases it occurs in association with intestinal celiac disease and responds to a gluten-free diet.
Dermatitis Herpetiformis - Tx
Dapsone and the Gluten-Free Diet
Dermatitis Herpetiformis - Key Features
Urticaria and symmetric, grouped vesicles on extensor surfaces, extremely pruritic
Benign and Pre-Malignant Epithelial Lesions
Seborrheic keratosis
Actinic keratosis
Seborrheic Keratosis - Pathogenesis
Acanthosis - thickened epidermis

Flat base demonstrates the "string sign" (i.e., the bottom of the lesion conforms to a horizontal line parallel to the epidermal surface)

Horn pseudocysts present
Seborrheic Keratosis - Morphology
Rough or waxy, variably colored (skin-colored, yellow, tan, brown, black), discrete papule or plaque

Superficial nature of lesion confers a "stuck-on" appearance

Size ranges from a few millimeters to several centimeters

Distributed commonly on the trunk, also extremities, sometimes face; spares palms, soles, and mucosae

*classic appearance do not need biopsy
Seborrheic Keratosis - Clinical Features
Generally older adults
• Benign
• Both genders
• All races, although more common among whites

• Rare for evolution to in situ squamous cell carcinoma can be identified histologically; less often, invasive squamous cell carcinoma and basal cell carcinoma
Actinic Keratosis - Pathogenesis
Precancerous lesion occurring on sun-exposed skin

Has potential to progress into tumor

Progresses to squamous cell carcinoma in situ, then invasive squamous cell carcinoma
Actinic Keratosis - Morphology
Usually less than 1 cm in diameter, tan-brown, red, or skin-colored and have a rough, sandpaper-like consistency

Erythematous, keratotic, thin papule on dorsal hand

Occurs on sun-exposed surfaces: scalp, face, ears, lower lips, dorsal hands, forearms

How it typically presents:
Actinic Keratosis - Clinical Features
Most commonly occurs in whites

Male predominance

Associated with fair skin (Fitzpatrick types I, II) and extensive sun exposure

Biopsied a lot to cancel out squamous cell carcinoma or basal cell carcinoma

In situ SCC: still in basement membrane
Invasive: down to the dermis (SCC)
Malignant Epidermal Tumors
Squamous cell carcinoma
Basal cell carcinoma
Squamous cell carcinoma - Pathogenesis
2nd most common cutaneous carcinoma in elderly

UV associated DNA damage

Immunosuppression

Tars & oils, arsenic, radiation, chronic ulceration, old burn scars,

P53 mutations

Xeroderma pigmentosum (dimers formed in skin not being removed)

<5% metastasize to regional lymph nodes

Can occur in various areas throughout body (often seen in oral mucosa and lungs, talking about skin here)

Skin not as aggressive as lung
Squamous cell carcinoma - Morphology
Sharply defined, red, scaling plaques.

More advanced, invasive lesions are nodular, and may ulcerate
Squamous cell carcinoma - Clinical Features
On biopsy of SCC, keratinization is often evident (as shown in this image) - keratin pearl formation

Can be completely excised typically
Basal cell carcinoma - Pathogenesis
Most common invasive cancer in humans (and most common in skin)

Incidence of basal cell carcinoma is increased in the setting of immunosuppression and in disorders of DNA repair, such as xeroderma pigmentosum

* LOF mutation in PTCH1, TSG negative regulator of Hedgehog signaling
Basal cell carcinoma - Morphology
Ulcerated nodules with rolled edges on the temple of an elderly man (rodent ulcer)
-Sclerotic waxy plaque with telangiectasia
-Scaly, erythematous, thin plaque with focal ulceration on the lateral neck, ill-defined borders
Basal cell carcinoma - Tx
Excision.

Mohs surgery is considered the most effective technique for treating BCCs and SCCs
Basal cell carcinoma - Clinical Features
Most common malignancy worldwide, is a locally aggressive tumor associated with mutations that activate Hedgehog signaling involve PTCH receptor protein

Peripheral nuclear palisading
Melanocytic Proliferations
Benign nevi (moles)
Dysplastic (Clark Nevi) or atypical nevi
Melanoma
Benign nevi (moles) - Pathogenesis
Developmental stages in the life history of common moles:
Junctional nevi--> compound nevi--> dermal nevi

Sequence occurs over decades and progression along the pathway may stop at any time

New lesions continue to appear into adult middle years

Smooth, color uniform throughout entire lesion

Progression:

Many have acquired mutations that lead to constitutive activation of NRAS of the serine/threonine kinase BRAF
Benign nevi (moles) - Morphology
Benign nevi (moles) - Clinical Features
Junctional Nevi
Compound Nevi
Dermal Nevi
Junctional Nevi
Rooted at basal layer forming a nest

Flat or slightly downward

Shape: initial pinpoint (1-2mm) and expands to 4-6mm

Smooth

Sharply circumscribed

Uniformly pigmented

Nevus cells at dermo-epidermal junction
Compound Nevi
Slightly elevated, dome shaped, papule

Flesh colored, brown, "halo nevus"

Nevus cells at dermo-epidermal junction and upper dermis
Dermal Nevi
Dome shaped, verrucoid (warty), pedunculated (on a stalk), sessile (broad based)

Brown, black, flesh colored, pink

Nevus cells in dermis, sometimes among fat cells
Dysplastic (Clark Nevi) or atypical nevi
Direct precursors of melanoma and when multiple in number are a marker of an increased risk for melanoma

Dysplastic Nevus Syndrome:
-lifetime risk for the development of melanoma in affected individuals is close to 100%
-sometimes develop several melanomas at multiple sites

ABCDE feature

Multiple atypical nevi
ABCDE Feature
1) rapid enlargement of a preexisting nevus
2) itching or pain in a lesion
3) development of a new pigmented lesion during adult life
4) irregularity of the borders of a pigmented lesion
5) variegation of color within a pigmented lesion
Melanoma
Malignant neoplasm of melanocytes

Strongly linked to acquired mutations linked to UV radiation in most cases

Readily cured when detected in early stages

High mortality rate in advanced stages
Melanoma - Risk Factors
UV exposure

Number of moles (both normal and atypical)

Fair skin, freckling, light hair

Fam history of melanoma

Immunosuppression

Age: risk increases with age

Gender: M>F

Xeroderma pigmentosum
Melanoma - Prognostic Factors
Tumor depth (the Breslow thickness)- most important

More than 90% of melanomas diagnosed in clinic are cutaneous

Cutaneous melanomas often harbor BRAF mutations (40-50%)
Melanoma - Management
AJCC TNM Cancer Staging required

Non metastatic disease- wide local excision (1-2cm margin):
->1mm in thickness- regional lymph node biopsy to evaluate for
-patients with melanoma in the initial node or nodes merit lymph node dissection in LN involvement
-interferon

Metastatic disease
-targeted agents- BRAF, MEK inhibitors
-Immunotherapy- anti-CTLA4, anti-PD1
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