Skin Pathology Flashcards
1
Q
What is the epidermis composed of and what are the 4 layers?
A
Comprised of keratinocytes
- Stratum basalis (basal): regenerative (stem cell) layer; to make new epidermis
- Stratum spinosum: characterized by desmosomes between keratinocytes (tightly connects cells; spinous processes)
- Stratum granulosum: characterized by granules in keratinocytes
- Stratum corneum: characterized by keratin in anucleate cells (top layer)
2
Q
What does the dermis consist of?
A
- Connective tissue,
- nerve endings
- blood and lymphatic vessels
- adnexal structures (e.g. hair shafts, sweat glands and sebaceous glands)
3
Q
What are five inflammatory dermatoses conditions?
A
- Atopic (eczematous) dermatitis
- Contact dermatitis
- Acne Vulgaris
- Psoriasis
- Lichen Planus
4
Q
- Characteristics of Atopic (Eczematous) Dermatitis?
- Where is it usually on body?
A
- Pruritic (itchy), erythematous, oozing rash, blistering vesicles and edema;
- often involves face and flexor surfaces
5
Q
Characteristics of Contact Dermatitis?
A
Pruritic, erythematous, oozing rash with vesicles and edema (similar to atopic dermatitis)
6
Q
How does contact dermatitis arise? Tx?
A
upon exposure to allergens such as:
- poison ivy and nickel jewelry (type IV hypersensitivity reaction; delayed cell mediated )
- Irritant chemicals (e.g. detergents)
- Drugs (penicillin)
- remove offending agent and topical glucocorticoids as needed
7
Q
How does acute contact dermatitis differ from urticaria?
A
- Urticaria:
- edema is restricted to superficial dermis
- Acute contact dermatitis
- edema seeps into the intercellular spaces of the epidermis splaying apart keratinocytes
- Mechanical shearing of intercellular attachment sites (desmosomes) causing formation of intraepidermal vesicles
8
Q
Photoeczematous Dermatitis? Cause what on skin?
A
- Photochemical reaction due to contact with a plant chemical and sun exposure
- Cause bizarre streaky pattern of blisters on sun exposed skin
- spontaneous resolution leaving long term hyperpigmentation
9
Q
Acne Vulgaris is characterized by?
A
- Comedones (whiteheads and blackheads),
- pustules (pimples)
- nodules (scars)
10
Q
Acne vulgaris is caused by? How are comedones formed
A
- Chronic inflammation of hair follicles and associated sebaceous glands
- Increase hormone=increase sebum production
- Excess keratin blocks follicles resulting in buildup
- Propionibacterium acnes produce lipases that break down sebum, create inflammation (comedones)
11
Q
- Characteristics on skin of Psoriasis?
- Usually found where on body?
A
- Well circumscribed, salmon colored plaques with silvery scale scaly patches
- on knees, scalp, lower back, penis
- pitting of nails may also be present
12
Q
What is Psoriasis due to? Associated with?
A
- Due to excessive keratinocyte proliferation with a possible autoimmune basis
- Associated with HLA-C
- Lesions often arise in areas of trauma (environmental trigger)
13
Q
Histology of Psoriasis shows what four features?
A
- Acanthosis (epidermal hyperplasia)
- Parakeratosis: hyperkeratosis with retention of keratinocyte nuclei in the stratum cornea= silvery scale)
- Munro microabscesses: Collection of neutrophils in the stratum cornea
- Thinning of the epidermis above elongated dermal papillae–> results in pin point bleeding when scale is peeled off (Ausptiz sign)
14
Q
What is Koebner phenomenon?
A
local trauma producing psoriatic like lesions
15
Q
Psoriasis has interactions between what cells? What does this produce?
A
- Complex interactions between CD4+ T cells, CD 8+ T cells, dendritic cells and keratinocytes
- Give rise to cytokine soup (e.g. TNF)
16
Q
Treatment of Psoriasis?
A
- Block TNF function (immunomodulant)
- corticosteroids
- UVA light with drug psoralen (PUVA) to damage keratinocytes
17
Q
Guttate Psoriasis (associated with what in young people)? Pustular Psoriasis
A
- Guttate psoriasis: Lesions appear as multiple small, red, raised, scaly patches usually all over trunk (* in young people following a strep throat infection)
- Pustular psoriasis: widespread area of pustules over trunk and limb (accumulation of neutrophils present directly beneath stratum corneum)—> fever and joint pain and may be life threatening
18
Q
Lichen Planus is characterized by (6 P’s)? Found where on body?
A
- Pruritic (itchy)
- planar (flat)
- polygonal
- purple
- papules
- plaques often with reticular white lines on their surface (Wickham striae- created by areas of hypergranulosis)
- Commonly involve wrists, elbows and oral mucosa
19
Q
Oral lesions of Lichen planus that persist for years are associated with?
A
Future probable oral squamous cell carcinoma
20
Q
Histology of Lichen Planus shows?
A
Inflammation of the dermal-epidermal junction with a “saw tooth” appearance.
21
Q
In pemphigus vulgaris autoantibodies are against? Cause blisters where?
A
Desmogleins 1 and 3 (dsg 1 and 3)
TYPE II HYPERSENSITIVITY cause blisters in the deep suprabasal epidermis
22
Q
In pemphigus foliaceus autoantibodies are against?
A
only Dsg 1
- lead to superficial subcorneal blister formation at the level of the lamina lucida of the basement membrane
23
Q
- How does Pemphigus vulgaris present as?
- where is it seen on the body?
A
- Skin and oral mucosa bullae
- Acantholysis (separation) of stratum spinosum keratinocytes (from Dsg1 and 3)
- Results in suprabasal blisters
24
Q
What does histology of pemphigus vulgaris show?
A
- Basal layer cells remain attached to basement membrane via hemidesmosomes (autoantibodies against desmoglein only)
- create “tombstone” appearance
25
Bullous Pemphigoid is autoimmune destruction of?
* **hemidesmosome**s between basal cells and the underlying basement membrane
* Due to **IgG** antibody against hemidesmosome component (BP180) of the basement membrane
26
What does Bullous Pemphigoid present as? Who does it typically affect?
* Blister between epidermis and dermis
* Usually seen in **elderly**
* Basal cell layers is detached from basement membrane
27
Immunofluorescence highlights what pattern in Bullous Pemphigoid?
IgG along basement membrane in a linear pattern
28
Dermatitis herpetiformis is due to?
* autoimmune deposition of **IgA** at the tips of dermal papillae
* antibodies cross react with **reticulin**
* component of the anchoring fibrils that tether the epidermal basement membrane to superficial dermis
29
What does Dermatitis herpetiformis present as? Where on the body?
* Pruritic vesicles and bullae (**very itchy!**)
* associated with the accumulation of nuetrophils (microabscesses) at the tips of dermal papillae
* grouped blisters on localized symmetrical extensor sites (elbows, knees)
30
What is dermatitis herpetiformis associated with?
**Celiac's disease**; resolves with a gluten free diet
31
* Epidermolysis Bullosa is a blanket term for?
* **Common feature?**
* Group of disorders caused by inherited defects in structural proteins that lend mechanical stability to the skin
* _Common feature_
* form blisters at sites of pressure, rubbing or trauma, at or soon after birth
32
Porphyria refers to?
A group of uncommon inbron or acquired disturbances of prophyrin metabolism porphyrin= pigment normally present in heme/myoglobin and cytochromes
33
Erythema multiform is what type of reaction? Characterized by?
* Hypersensitivity reaction
* characterized by targetoid rash and bullae
* Targetoid appearance is due to central epidermal necrosis surrounded by erythema
34
What is Erythema multiforme (EM) most commonly associated with? Other associations?
* **HSV infection**
* also associated with:
* Mycoplasma infection
* drugs (penicillin, sulfanomides)
* autoimmune disease (SLE)
* malignancy
35
Erythema Multiforme with oral mucosa/lip involvement and fever is termed?
**Stevens- Johnson syndrome (SJS)**
Toxic epidermal necrolysis (TEN) is a severe form of SJS characterized by diffuse sloughing of skin, resembling a large burn most often due to adverse drug effect
36
* Granuloma annulare is characterized by what kind of lesions?
* Associated with?
* Benign self-limited dermatosis (hands and legs)
* characterized by raised annular lesions
* associated with morphea, **chronic Hep C** infection, autoimmune thryoiditis
37
* Characteristic of Verruca (warts)?
* Association with?
* Common location?
* Flesh colored papules with a rough surface (raised)
* Hands and feet are common location
* Associated with **HPV** infection of keratinocytes
38
* Characteristic of Molluscum Contagiosum?
* Due to?
* What do affected keratinocytes show?
* Firm, pink, umbilicated papules
* due to **poxvirus**
* _Hallmark_\*: affected keratinocytes show cytoplasmic inclusions (molluscum bodies)
39
Impetigo is infection most often due to which bacteria?
* **S. aureus or S. pyrogens**
* S. aureus produce exfoliative toxins A and B that cleave desmoglein 1 (desomosomes)
40
Who does Impetigo most commonly affect?
Children, very contageous
41
What does Impetigo present as?
* Erythematous macules that progress to pustules, **usually on the face**
* Rupture of pustules results in erosions and dry, crusted, honey colored serum
42
As opposed to deep fungal infections of the skin where dermis or subcutis is primarily involved, **superficial fungal infections of skin are confined to?**
Confined to stratum corneum and are caused primarily by **dermatophytes**
43
* Cellulitis is due to?
* Risk factors?
* Presents as?
* Deeper (dermal and subcutaneous) infection
* **S. aureus or Strep. pyogenes**
* risk factors:
* recent surgery, trauma or insect bit (introduce bacteria into dermis)
* presents as red, tends, swollen rash with fever
44
What can Cellulitis progress to?
**Necrotizing fasciitis**
45
Staphylococcal Scalded Skin Syndrome is caused by?
* epidermolysis of what skin layer?
* **S. aureus infection**
* exfoliative A and B toxins result in epidermolysis of the stratum granulosum (separate stratum granulosum from rest of skin)
* sloughing of skin with erythematous rash and fever; lead to significant skin loss
46
How is Staphylococcal Scalded Skin Syndrome distinguished histologically from toxic epidermal necrolysis?
* By level of skin separation
* Separation in TEN occurs at the dermal-epidermal junction (deeper separation)
* as opposed to stratum granulosum (Scalded skin syndrome)
47
* Where are melanocytes located?
* Responsible for?
* Within the **epidermis**
* responsible for production of **melanin**
* a brown pigment that absorbs and protects against potentially injurious UV radiation in sunlight
48
* Where are melanocytes derived from?
* In what organelle do they synthesize melanin?
* What do they use as a precursor molecule?
* Derived from **neural crest**
* Synthesize melanin in melanosomes using _tyrosine_ as a precursor molecule
* Pass melanosomes to keratinocytes to become pigmented
49
Freckle (Ephelis) is due to?
* benign lesion of sun exposed skin
* associated with fair skin and red hair (darkens when exposed to sunlight)
* Due to **increased number of melanosomes** (melanocytes are _NOT_ increased)
50
Cafe au lait spots are associated with? How are they different than freckles?
* **neurofibromatosis**
* Different than freckles because they are larger and arise independently of sun expsoure
51
Melasma (aka chloasma, mask of pregnancy) is due to?
* **Increase in epidermal melanin** but _no_ increase in number of melanocytes
* darkened skin due to hormonal changes (mask like)
52
Vitiligo presents as? Due to?
* Partial or complete loss of pigment producing **melanocytes**
* Due to autoimmune destruction of melanocytes
* more noticeable in dark skinned individuals
53
* Rosacea characterized as?
* Associated with?
* Phymatous rosacea can cause?
* Inflammatory facial skin disorder characterized by erythematous papules and pustules but no comedones
* Associated with facial flushing in response to external stimuli (e.g. heat or alcohol)
* Phymatous rosacea can cause rhinophyma (bulbous deformation of nose)
54
* Seborrheic keratosis appears as?
* Caused by which activating mutation?
* Occurs where on body?
* Common in which population?
* Common benign neoplasm of older persons
* activating mutation in **FGFR3**
* Flat, greasy, pigmented squamous epithelial proliferation with keratin filled cysts
* looks "stuck on"; tan/ dark brown velvety lesions
* occur on head, trunk and neck
55
Leser-Trelat sign? Indicates what underlying condition?
* sudden appearance of multiple seborrheic keratoses,
* indicating underlying malignancy (GI)
56
Acanthosis nigricans is due to? Associated with?
* Epidermal hyperplasia
* causes symmetric, hyperpigmented thickening of skin
* especially in axilla or on neck
* _Associated with:_
* i**nsulin resistance** (e.g. diabetes, obesity, Cushing syndrome)
* visceral malignancy (especially **gastric carcinoma)**
57
What germline mutation is associated with familial forms of melanoma?
* **CDKN2A**
* encodes two protein products:
1. _p16/INK4_ a cyclin dependent kinase inhibitor that reinforces RB checkpoint
2. _p14/ARF_ which activates the p53 pathway by inhibiting MDM2
58
* Albinism is due to?
* May involve which parts of the body?
* Congenital lack of pigmentation due to an **enzyme defect that impairs melanin production**
* May involve eyes (ocular form) or both eyes and skin (oculocutaneous form)
59
Albinism has an increased risk to which cancers? Why?
* Squamous cell carcinoma
* basal cell carcinoma
* melanoma
* due to reduced protection against UVB
60
Nevus (mole) is?
* Nevus (mole) is benign neoplasm of melanocytes
61
How does an acquired Nevus (mole) form?
* Begins as nests of melanocytes at the dermal-epidermal junction **(junctional nevus**); common in kids
* grows by extension into dermis (**compound nevus)**
* junctional component is eventually lost resulting in an **intradermal nevus** which is the most common mole in adults
62
Dysplastic nevus is a precursor to? Characteristics of dysplastic Nevi?
* precursor to **melanoma**
* Flat macules, slightly raised with a "pebbly" surface, or target like lesions with a darker raised center and irregular flat periphery
63
How can you differentiate between seborrheic keratosis and melanoma?
**horn cysts** are only in seborrheic keratosis
64
What distinguishes dysplastic nevi from typical melanocytic nevi?
Additional inherited loss of function mutations in **CDKN2A** in dysplastic nevi
65
Definition of melanoma?
**Malignant neoplasm of melanocytes**; most common cause of death from skin cancer
66
What are risk factors for melanoma?
* Based on UVB induced DNA damage
1. prolonged exposure to sunlight
2. albinism
3. xeroderma pigmentosum (defect in nucleotide excision repair enzyme)
_additional risk factor is_:
* dysplastic nevus syndrome
67
Melanoma presents as a mole like growth with "ABCD"?
* A= Asymmetry
* B= Borders are irregular (scalloped)
* C= Color is not uniform (various shades of brown, black, red)
* D= Diameter \> 6 mm
68
Melanoma is characterized by what two growth phases?
1. Radial growth **horizontally** along the epidermis and superficial dermis;
* low risk of metastasis
2. **Vertical** growth into the deep dermis
* increased risk of metastasis
69
In melanoma what is the most important prognosis factor?
Depth of extension (deeper into dermis=worse)
* i.e. **Breslow thickness**
70
_Melanoma variant_: **superficial spreading**
* Prognosis?
* Spreading?
* Most common subtype
* Dominant **early radial growth**= good prognosis
71
_Melanoma variant:_ **Lentigo maligna melanoma**
* prognosis/spreading?
* **radial growth**: remain along dermal-epidermal junction
* good prognosis
72
_Melanoma variant_: **nodular**
* spreading and prognosis?
* early **vertical** growth
* grows down into dermis and pushes epidermis up= nodular on skin
* poor prognosis
73
_Melanoma variant:_ **Acral lentiginous**
* arises where on body?
* Often seen in?
* Not associated with?
* arises on the palms or soles (acral)
* often associated with dark skinned individuals
* **NOT** associated with UV light exposure
74
Basal cell carcinoma definition?
**Malignant proliferation of the basal cells** of the epidermis
most common cutaneous malignancy
75
Risk factors for basal cell carcinoma?
* UVB induced DNA damage
* prolonged exposure to sunlight
* albinism
* xeroderma pigmentosum (defect in nucleotide excision repair enzyme; can't fix pyrimidine dimers)
76
* What is the classic presentation of basal cell carcinoma?
* Where does it present on body?
* Elevated nodule with a central, ulcerated crater surrounded by dilated (**telangiectatic**) vessels; "pink, pearl like papule"
* classic location is **upper lip**
77
Histology of basal cell carcinoma?
Shows nodules of basal cells with peripheral palisading (lining up)
78
Treatment of basal cell carcinoma?
Surgical excision; metastasis is rare
79
Squamous cell carcinoma definition? Characterized by?
* Malignant proliferation of squamous cells
* characterized by formation of **keratin pearls**
80
Risk factors of squamous cell carcinoma?
* UVB induced DNA damage
* prolonged exposure to sunlight
* albinism
* xeroderma pigmentosum
_Additional risk factors include:_
* **HPV**
* immunosuppression, chronic ulcers, burns
81
How does squamous cell carcinoma present? Associated with? What is the treatment?
* ulcerated red lesions nodular mass usually on the face
* classically involving the **lower lip**
* associated with **chronic draining sinuses**
Treatment is excision; metastasis is uncommon
82
* What is Actinic/ Solar keratosis?
* Presents as?
* Associated with?
* Treatment?
* Premalignant lesion of squamous cell carcinoma
* presents as small, rough erythematous or brownish (cutaneous horn), scaly plaque
* often on face, back or neck associated with sun damage
_Treatment_:
Curettage, cryotherapy, topical chemo (Imiquimoid, 5-FU)
83
* What is Keratoacanthoma?
* presents as?
* **Variant of squamous cell** carcinoma:
* well differentiated
* develops rapidly and regresses spontaneously
* presents as a cup shaped tumor **filled with keratin debris** in center
84
Bowen's Disease (SCC in situ) presents as?
* Sharply defined, red, scaling plaques that are slightly raised with irregular border
* in **penile shaft**
* No invasion of basement membrane
85
Genetics of Basal Cell Carcinoma?
* Hedgehodge signaling pathway
* mutated **PTCH** gene---\> leads up upregulated cell division leading to abnormal growth (basal cell carcinoma)
86
Pathogenesis of Urticaria?
* Mast cell dependent
* IgE dependent (type 1 hypersensitivity)
87
What is morphology of urticaria?
* Erythmatous, edematous circular plaques (**wheals**)
* dermal edema
* normal epidermis
88
* What type of hypersensitivity reaction is Atopic dermatitis?
* Associated with?
* **Type 1 hypersensitivity** reaction
* associated with asthma and allergic rhinitis
89
Treatment of acne vulgaris?
* Benzyl peroxide (antimicrobial)
* Extreme case: antibiotics Vitamin A derivative (**isotreinoin**): antisebacious action---\> decrease keratin
90
Lichen planus is associated with?
**Hepititis C virus (HCV)**
91
Seborrheic Dermatitis is associated with what superficial fungus?
* Malassezia spp.
* *Pityosporum ovale*
* **hypersensitivity reaction to superficial fungi
92
Clinical presentation of seborrheic dermatitis?
Mainly on scalp some on face itchy, scaly growth, macule, papules
93
Treatment of seborrheic dermatitis?
**Ketaconazole**
94
* Erythema Nodosum is a form of?
* Associated with?
* **Panniculitis**
* inflammatory lesion is subQ fat- result in erythematous nodules
* Associated with **irritable bowel syndrome (IBS)**
95
Erythema Nodosum is associated with?
* coccidiodomycosis
* histoplasmosis
* TB and leprosy
* Strep. pharyngitis
* Pregnancy
96
What is clinical presentation of erythema nodosum? Where is it on part of body?
* Raised and painful erythematous nodule
* usually located anterior shin
97
Discoid lupus erythematosus (skin only) is what kind of disorder? Who does it main effect
* Autoimmune
* Affects women more than men
* risk factor is also sun exposure
98
What happens to the basal layer in discoid lupus erythematous?
* degeneration of basal layer
* Flask shaped plugs of stratum corneum
99
* Clinical presentation of discoid lupus erythematous (skin only)?
* Tx?
* Red inflamed patch with scaling and crusty
* Treat with corticosteroids
100
Treatment of Melanoma?
* Surgical excision with wide repairs
* If have *BRAF V600E* mutation treat with **vemurafenib**, a BRAF kinase inhibitor.
101
* Pityriasis rosea affects who?
* Arises where on the body?
* How does it resolve?
* "Herald patch"
* followed days later by other scaly erythematous patch
* Christmas tree distribution on trunk
* Multiple plaques with collarrett scale
* Affects women
* Self resolving 6-8 weeks
