Derm I-III & Clinical Derm

Question 1

What are the three basic cutaneous layers (in order from top to bottom)

Answer 1

1. epidermis
2. dermis
3. subcutis “fatty layer”

• each layer has components that can be involved in pathology-the name of the path is usually linked to the structure where it occurs

Question 2

What are the components of the epidermis (my MLK)

Answer 2

• composed mainly of keratinocytes with melanocytes, merkel cells, and Langerhan cells interdispersed.
• Keratinocytes mature through a process called desqumatization where they rise from the basal layer to the cornified layer in 25 days.
• major layers have histologic differences seen by light microscopy. (cancel lab, get some beer)
  
  • Stratum Corneum
  • Stratum Lucidum (thick skin only, palms and soles of feet)
  • Stratum Granulosum
  • Stratum Spinosum
  • Stratum Basale

Question 3

What are the components of the dermis

Answer 3

• directly beneath the epidermis.
• composed of the papillary dermis and the reticular dermis.
  
  • diff elastic fiber composition but no true anatomic separation.
• papillary dermis is flanked by the epidermal rete and contains blood vessels and Meissner’s corpuscles.
• reticular dermis is everything beneath the papillary dermis up to the subcutaenous adipose tissue.
  
  • houses the adnexel structures of the skin as well as small vessels (mostly capillaries) and nerves.
• *List:
  
  • sebaceous glands
  • hair follicles
  • pilar muscle
  • eccrine/apocrine glands
  • small vessels
  • fibrohistiocytes

Question 4

what are the components of the subcutis

Answer 4

• adipose tissue
• larger vessels (with smooth muscle a/r the vein)
• nerves including the Pacinian corpuscles.

Question 5

Define HYPER-keratosis

Answer 5

thickening of the stratum corneum (outermost layer of epidermis)

Question 6

Define Para-keratosis

Answer 6

Flattened, keratinocyte nuclei within the stratum corneum, where nuclei are not normally present

Question 7

Define Ortho-keratosis

Answer 7

Hyperkeratosis of anuclear keratinocytes within the stratum corneum

Question 8

Define Acanthosis

Answer 8

thickened stratum spinosum

Question 9

Define Acantho-lysis

Answer 9

• Loss of cohesion between keratinocytes d/t dissolution of intercellular connections.
• Keratinocytes separate and “round up” (versus in spongiosis, where keratinocytes stretch and elongate)

Question 10

Define Dys-keratosis

Answer 10

Abnormally or prematurely cornified (keratinized) keratinocytes in the epidermis that stain pink on H & E

Question 11

Define Spongiosis

Answer 11

• Intercellular edema between keratinocytes.
• Edema may cause keratinocytes to become elongated and stretched, hallmark of eczema
  
  • (spongebob squarepants is in the hallway of exes)

Question 12

Define Papillomatosis

Answer 12

irregular undulation of the epidermal surface

Question 13

What are the (6) different types of dermal change and their definitions?

Answer 13

1. dermal atrophy-decreased thickness of dermis
2. Edema-accumulation of interstitial fluid
3. solar elastosis-accumulation of basophilic (grey/blue) material in the upper dermis d/t sun damage
4. hyalinization-accumulation of dense, eosinophilic (stains pink/red) acellular material
5. sclerosis-hyalinized collagen with decreased fibroblasts
6. mucin-dermal mucin contains acid mucopolysaccharide and stains pale blue, smudgy, threadlike, or granular on H&E

Question 14

Clinical changes and their descriptions

Answer 14

• wheal-transient papule/plaque
  
  • papule-elevated skin lesion <1cm
    
    • plaque-papule>1cm
  • macule-flat discoloration <1cm
    
    • patch-macule >1cm
• excoriation-small superficial defect involving epidermis and papillary dermis
  
  • results from localized trauma like picking or scratching
  • Ulcer-loss of epidermis and dermis (and sometimes deeper tissue)

Question 15

What are the (3) disorders of desquamation?

Answer 15

1. ichthyosis vulgaris
2. lamella ichthyosis
3. X-linked ichthyosis

Question 16

Epidermal maturation-desquamatization

Answer 16

• layers of epidermis represent VERTICAL maturation from un-differentiated basal cells to fully differentiated cornified cells
• from basal cell to cornified cell takes 25 days (lower level moves to top)
  
  • shorter maturation pd in inflamm conditions
  • keratin production also changes as the cell matures and disruption in the mechanism can effect the integrity of the keratinocytes
  • disordered maturation causes skin thickening due to lack of desquamation

Question 17

Ichythosis-(4)Disorders of Desquamatization

Answer 17

• defective desqumatization leads to a build up of compacted scale
• mostly hereditary disorders that appear at birth
  
  • Ichthyosis vulgaris (AD) or acquired
  • most of the baby forms are AR:
    
    • congenital ichthyosiform erythroderma
    • lamellar ichthyosis (AR)
    • X-linked ichthyosis: deficiency in steroid sulfatase (enzyme that helps skin shed)

Question 18

Ichthyosis Vulgaris

Answer 18

• disorder of dry, scaly skin; “fish scales”
• Histo:
  
  • orthokeratosis (Hyperkeratosis/thickening of anuclear keratinocytes within the stratum corneum)
  • thinning or loss of granular layer
• diagnosed clinically by looking at the skin
• passed down through families AD
  
  • caused by a defect in the FLG gene, which synthesizes the microfilament filaggrin.
• Will be more prominent in winter
• tx: heavy duty moisturizers, creams, ointments > lotions.

Question 19

Lamella ichthyosis

Answer 19

• Mostly affects palms, soles, and flexures.
• AR; associated with a mutation in keratinocyte transglutaminase.

Question 20

X-linked ichthyosis

Answer 20

• presents as brownish and scaly eruption in males, usually early childhood.
• More likely to involve flexural creases than ichthyosis vulgaris.
• Associated with deficiency in STS gene which makes steroid sulfatase

Question 21

What are the (3) main benign epithelial neoplasms?

minor guy?

Answer 21

1. seborrheic keratosis
2. acanthosis nigricans
3. fibroepithelial polyp/achrocordon/skin tag
4. (Epidermal inclusion cysts/Wen)

Question 22

Seborrheic Keratosis (SK)-gross

Answer 22

• “Stuck-on,” waxy appearing brown papules or plaques anywhere on the skin except for the palms and soles
• usually well circumscribed around border
• generally on pts >30 yo

Question 23

Seborrheic keratosis (SK)-Histo

Answer 23

• Key features of seborrheic keratosis:
  
  • Hyperkeratosis
  • epidermal acanthosis (thickened)
  • composed of uniform small keratinocytes with:
    
    • flat base “String sign”
      
      • if it was malignant would be fingering down
    • keratin filled “horn cysts”.
  • Frequent melanin pigment present

Question 24

Seborrheic keratosis (SK)-General

Answer 24

• epidermal papillomatosis, acanthosis, and horn cyst formation.
  
  • ep=skin surface elevation caused by hyperplasia and enlargement of contiguous dermal papillae
• Present as stuck on plaques or verrucous lesions
• most common on head/neck/trunk (but can be seen anywhere.)
• Considered a growth of aging-these are benign lesions.
  
  • Seldom seen in young patients.
• 100s may be seen as pt of a paraneoplastic syndrome in patients with metastatic cancer = Leser-Trélat sign***.

Question 25

Acanthosis Nigricans-General

Answer 25

• may look similar to a seborrheic keratosis but lacks acanthosis and horn cyst.
• Seen in all ages, can be associated with insulin resistance and malignancy.
• Clinically presents as a velvety plaque most common on the back of the neck or axilla.

Question 26

Acanthosis Nigrican-Histo/Gross

Answer 26

• gross: Velvety, papillomatous, hyperpigmented plaques, commonly found in the creases of the axilla and neck
• Histo: **papillomatosis, hyperkeratosis, basal layer hyper-pigmentation (can also have that with SK from the melanin)

Question 27

Seborrheic keratosis (SK) vs. Acanthosis Nigricans (ANig)

Answer 27

• SK:
  
  • middle age and up
  • roundish, flat or coin-like waxy plaques with velvety surface
  • acanthotic hyperkeratosis, horn cysts, increased melanin
  • Leser-Trelat sign=parananoplastic syndrome
    
    • sudden onset of SK, may have malignancy
• ANig:
  
  • benign type=childhood
    
    • obesity/endocrine
    • hereditary
  • malignant type=middle age and up
    
    • can have other internal malignancies and secondarily get these velvety patches
  • epidermal papillomatosis, increased melanin

Question 28

Fibroepithelial Polyp (Achrochordon)/Skin Tag-General

Answer 28

• benign polypoid growths most common at sites of rubbing/friction.
• composed of an outgrowth of fibroblasts and collagen with vessels covered with normal or acanthotic epidermis

Question 29

Fibroepithelial Polyp (Achrochordon)/Skin Tag-Histo/Gross

Answer 29

• Histo: more adipose tissue and vessels creating polyp-loose stroma
• papillomatosis (skin surface elevation caused by hyperplasia and enlargement of contiguous dermal papillae)-may or may not

Question 30

Epidermal inclusion cysts/Wen:

Answer 30

• Not epidermal neoplasms at all but categorized here because of the misnomer in their name.
• Actually are follicular cysts composed of the infundibular portion of the hair follicle (similar to nml epidermis with the exception of a loss of rete pegs).
• Makes keratin (like epidermis) and thus appears as a keratin filled cystic structure lined by epidermis.
• Most do not communicate with the epidermis and are therefore dermal based nodules.

Question 31

What are the BIG THREE pre-malignant and malignant epithelial neoplasms?

Answer 31

1. Actinic keratosis (AK)-pre
2. Squamous cell carcinoma (SCC)-mal
3. basal cell carcinoma (BCC)-mal

Question 32

Actinic Keratosis (AK)-General

Answer 32

• earliest identifiable lesion that can eventually develop into an invasive squamous cell carcinoma (SCC).
• lesions diagnosed in 14% of all visits to dermatologists, following only acne and dermatitis in frequency.
  
  • increasingly common with age
• typically produced by UV radiation, but ionizing radiation, arsenic, or polycyclic hydrocarbon exposure may also cause them.
• PE: the typical AK is a poorly-demarcated, scaly slightly erythematous patch found on sun-exposed/damaged skin areas:
  
  • face, balding scalp, posterior neck, and dorsal upper extremity.
  • feel rough or “gritty”, may be difficult to see.

Question 33

Actinic Keratosis (AK)-Tx

Answer 33

• tx with cryotherapy or topical chemotherapeutic to prevent progression to SCC

Question 34

Actinic Keratosis (AK)-Histo and Gross

Answer 34

• T-cell lymphocytes ae the inflamm cells of the skin, look very blue
• acute condition-lots of T-lymphocytes
  
  • can get neutrophils with ulcerations or cuts
• Gross: ill-define scaly erythematous macules
• Histo: some blebbing
  
  • **solar elastosis**–due to sun damage
  • basal layer atypia with overlying parakeratosis alternating with orthoparakeratosis (=Hyperkeratosis of anuclear keratinocytes within the stratum corneum); (flag=another soft sign)
  • melanin sits in basal layer and acts as sunshade, protects lower levels from sun damage

Question 35

Squamous Cell Carcinoma (SCC)-General

Answer 35

• 2nd most common cutaneous skin tumor
• SCC are generally erythematous, scaly papules or plaques with ill-defined borders, may be confused with large, hypertrophic AKs (differentiate with biopsy)
• Microscopically, SCC: proliferation of pleomorphic keratinocytes confined to the epidermis (SCC in-situ) –or– extending into the dermis (invasive SCC).

Question 36

Squamous Cell Carcinoma (SCC)-Etiology

Answer 36

• sun-exposed sites, older indivs; M>F
• <5% metastasixe
• AK=precursor lesion of SCC. BUT, some SCCs develop de novo and do not form from a previous AK.
• Keratinocytes with one **TP53** mutation after UV radiation may undergo apoptosis.
  
  • often seen at pyrimidine dimers (Xeroderma pigmentosum)
  • if keratinocytes with mutated p53 suffer a 2nd hit or mutation, become resistant to further apoptosis, undergo clonal expansion=AKs
  • Uncontrolled proliferation of these abnml keratinocytes leads to the development of invasive SCC.
• Other causes:
  
  • activating mutations in HRAS
  • los of fxn mutations in Notch receptors
  • immunosuppression, specifically HPV5 and 8
  • other: industrial, chronic wounds, burn scars, arsenic, ionizing radiation

Question 37

Squamous Cell Carcinoma (SCC)-Clinical Manifestations

Answer 37

• SCCs usually present as firm, skin-colored to pink, papules or plaques, commonly found on head/neck region of elderly indivs.
  
  • Other locations: trunk, arms, dorsal hands and legs.
• Hyperkeratosis, ulceration or crusting may be found on its surface.
  
  • sometimes verrucous papules and nodules
• Symptoms: itching, pain and bleeding may be associated with the lesion.

Question 38

Squamous Cell Carcinoma (SCC)-Histo

Answer 38

• proliferation of (islands) atypical keratinocytes (squamous pinkish cells) that extend from the epidermis invading into the dermis with an uneven base
• proliferation of cells can be seen as slender, long strands or as bulky masses.
• Indiv cells have a glassy eosinophilic cytoplasm, with large nuclei.
• Mitotic figures and keratin pearls (with retained nuclei) are also seen.
• Various degrees of differentiation may be seen and is usually described as well-, moderately-, or poorly differentiated.
• Increasing degrees of malignancy show:
  
  • less demarcation between the tumor masses and the stroma,
  • greater atypia, less keratinization, and loss of intercellular bridges.
• Other histologic variants: acantholytic, adenosquamous, spindle-cell, verrucous, and desmoplastic SCC.

Question 39

Squamous Cell Carcinoma (SCC)-Tx

Answer 39

• Excision for low risk SCCs (<2 cm diameter, well differentiated)
• Mohs micrographic surgery
• Radiation therapy (used in combo with other modalities for aggressive, recurrent, or large inoperable tumors)
• Cryotherapy (for small, superficial, or low-risk lesions)

Question 40

SCC in situ (Bowen’s Disease)

Answer 40

• **Full thickness atypia, basal layer sparing (“eyeliner sign”), may show skip areas but involves follicles (in contrast to AKs)
• no invasion into the dermis (in contrast to SCC).
• Bowen’s Disease: atypia at all levels of the epidermis.
  
  • Clinically a plaque-like lesion
  • needs to be excised!
• BoweNOID Papulosis: similar histo as Bowen’s Disease.
  
  • **HPV-induced, located on the genitals
  • may spontaneously regress/progress
  • Frequently multiple papules

Question 41

Basal Cell Carcinoma (BCC)-General

Answer 41

• most common non-melanoma skin cancer (80%)
  
  • most common invasive cancer in humans
• more common in men (2:1)
• RF:
  
  • older indivs
  • UV sun exposure
  • fair skin
  • immunosuppressed
  • FHx of skin cancer, radiation therapy
  • genetic (DNA mismatch) syndromes
    
    • nevoid BCC syndrome, xeroderma pigmentosa

Question 42

Basal Cell Carcinoma (BCC)-Clinical Manifestation

Answer 42

• Sun-exposed areas=most frequent location of BCCs
  
  • but it can be found in anywhere in the skin.
• subtypes: nodular BCC and superficial BCC
• Gorlin syndrome (i.e. Nevoid Basal Cell Carcinoma syndrome) is characterized by:
  
  • multiple BCCs during childhood (before 20yo)
  • odontogenic keratocysts (of the jaw and skeletal defects)
  • Tumors associated with this dz: medulloblastoma, ovarian fibromas

Question 43

Basal Cell Carcinoma (BCC)-Gross

Answer 43

pearly, pink papule with overlying telangiectasia

Question 44

Basal Cell Carcinoma-Histo

Answer 44

• blue cells, with picket-peripheral palisading
• retraction artifact-secondary to processing, seperate from surrounding dermis
• nodular type: islands of basaloid cells in the dermis

Question 45

Basal Cell Carcinoma (BCC)-Etiology

Answer 45

• UVB damages the DNA, produces C-T transition mutations.
• p53 and ***PTCH (patch) genes are the major targets of UVB for the development of BCC.
  
  • p53=tumor-suppressor gene
    
    • regulates cell cycle and apoptosis
    • mutated in 56% of human BCC.
  • PTCH gene (chrom 9q22) regulates Hedgehog signal transduction pathway
    
    • “2 hit” hypothesis
    • mutated in 30-40% of sporadic Nevoid BCC i.e Gorlin syndrome.
  • In 50% of BCCs isolated from xeroderma pigmentosa both p53 and PTCH genes are mutated.
• UV radiation induces a state of relative immunosuppression (by altering antigen-presenting mechanisms and producing immunosuppressive cytokines) that ultimately compromises tumor rejection.

Question 46

Sample Question : An 65 year old, Caucasian male patient present to dermatology clinic for an annual skin check. He has an occupational history as a banking executive. He splits his time between your suburban city (were they reportedly have high chlorine levels in the water system) and his near by lake home. He was very active until a chronic lower leg ulcer secondary to his severe diabetes has been affecting him the last couple of years and he reports a recent 20 pound weight gain since. His risk factors for squamous cell carcinoma include

Answer 46

Answer: Age, gender, exposure to UVB rays, chronic cutaneous wound

Question 47

Sample Question: A 13 year old patient present with 2 separate nodules that you biopsy and the path report demonstrates a proliferation of basaloid cells extending from the lowest level of the epidermis into the dermis. This patient’s tumor likely has which of the following genetic mutations

Answer 47

Answer: Familial mutation in either PATCH (*BCC) or TP53 (secondary mutation) genes

Question 48

Sample Question: Recently your Aunt has been diagnosed with cutaneous SCC. She comes to you (the family doctor) to ask what is the likely cause and outcome of her diagnosis? Which of the following is the best statement about SCC of the skin?

Answer 48

Answer: SCC is directly associated with sun exposure. Tx: local excision. <5% metastasize.

Question 49

What are the (4) tumors of Melanocytes

Answer 49

1. Freckle (ephelis)
2. Lentigo
3. Melanocytic Nevi
4. Melanoma

Question 50

Freckle (ephelis)-Tumor of Melanocytes

Answer 50

• Small, tan-red to light brown macules (flat lesions) on sun-exposed areas.
• Most common lesion of childhood.
• Increased melanin pigment within basal keratinocytes
• Melanocytes may be enlarged (hyperplasia) but nml density

Question 51

Lentigo-Tumor of Melanocytes

Answer 51

• small, oval tan-brown
• mucous membranes in any age
• melanocytic hyperplasia along the basal layer

Question 52

Melanocytic Nevi-Tumor of Melanocytes

Answer 52

• Nevi=NESTS of melanocytes
• Tan to brown macules and papules.
• Common type: Junctional, compound and intradermal: nests of melanocytes
• “Dysplastic” Nevi – single and cytologically atypical melanocytes, in addition to nests with architectural atypia.
  
  • dysplastic is controversial term because it implies gradation to malignancy
• papules/macules tend to arise in adolescence; start in epidermis as junctional then melanocytes move down into the dermis
  
  • becomes more compound and intradermal with age

Question 53

Melanoma-Tumor of Melanocytes

Answer 53

• Most >10 mm, changes in color, size, shape of previous lesion. Variations in color. ABCDEs.
• Nests and single malignant (tumor)melanocytes cells

Question 54

Melanocytes

Answer 54

• cant see on nml skin
• clearish cells in basal layer with dark angulated nuclei; ratio 1:10 (melanocytes to basal layer keratinocytes)
  
  • melanocyte hyperplasia-lots of sun exposure will increase ratio
• darker skin does NOT mean more melanocytes, means the ones you have are more ACTIVE, make more melanin
  
  • melanosome in the melanocyte passes the pigment to keratinocyte
  • pigment hats over nuclei in keratinocytes protect genetic material by blocking out UV radiation
• Melanocytes are derived from neuroectoderm
• fxn: produce melanin pigment with tyrosinase.

Question 55

Intradermal (common) Melanocytic Nevus (IDN)

Answer 55

nests of melanocytes are confined to the dermis

Question 56

Dyplastic Nevi-Histo

Answer 56

• will always have activity at the epidermis
• will have fiberplasia lines in pink stuff aroun melanocytes
• enlarged melanocytes at the (basal layer of epidermis) dermal-epidermal junction (DEJ) increased in numbers and bridging of melanocytes
• disordered histological architecture, typified by less circumscription of the nevus cell nests and extension of the junctional nests beyond the intradermal component.
• nests that vary in size, shape, and spacing.
• upper dermis usually shows fibrosis and contains a host response of lymphocytes.

Question 57

Dysplastic Nevi-General

Answer 57

• **looks like melanoma but its not!
• 1978 by Clark: usually greater than 5 mm, flat to slightly raised macules, sun-exposed and protected areas.
• **Architecturally atypical: melanocytic nests may be larger and fused = bridging (ODD!), and junctional component extends past dermal components = shouldering.
• Single melanocytes along DEJ
• Cytologic atypia – enlarged, angulated nuclear contours, hyperchromasia
• Vast majority of lesions are clinically stable thus best considered as a risk factor for melanoma.
• ***Dysplastic Nevus Syndrome – (<10% of pts) tendency to develop multiple dysplastic nevi and melanoma.
  
  • 50% have melanoma by 60yo
  • ​(b/c melanomas come from melanocytes, so high density of the latter=anyone of them can turn on and go bad)
  • AD, ***CDKN2A*** gene on chromosome 9p21 (and CDK4 on chromosome 12q14)

Question 58

Melanoma-General

Answer 58

• deadly skin cancer.
• Early recognition and surgical excision is critical.
• ABCDE
  
  • A=Asymmetrical
  • B=Border-irregular, notched, blurred, uneven
  • C=Color, uneven-shades of brown, tan, blk, red, white, blue
    
    • areas of regression may be noted
  • D=Diameter: melanomas grow in dimater and usually are larger in diameter than the size of a pencil eraser (6mm) in 95% of cases
  • E=Evolving: changes in size, shape, color, levation, or new symptoms: bleeding, pruritus, pain
• Prognostic factors:
  
  • ****depth (Breslow)****
    
    • ​measured by an ocular micrometer, from the top of the granular layer of the epidermis to the base of the neoplasm
  • # of mitotic figures (thin melanomas)
  • ulceration.
• Sentinel lymph node biopsy: positive is poor prognostic indicator.
  
  • usually done at 0.8mm depth

Question 59

Melanoma Histopath

Answer 59

• Radial (epidermis highly involved) growth phase: Lentigo maligna, superficial spreading, acral/ mucosa lentigenous
• Vertical growth phase: Nodular or progression (entirely dermal, small epidermal) of radial growth phase melanoma implies metastatic potential.
• ***Depth of invasion: in mm***
• Mitotic Counts: per mm2
• ** All types of melanoma can transition to a vertical growth phase over time (sans tx) hence early diagnosis and tx is key to increase disease free survival.

Question 60

Melanoma-Histo 1/3

Answer 60

• Malignant melanocytes are invading into the dermis as a nodule of spindle cells.
• Melanin pigment can be seen.
• overlying epidermis has nests (full thickness) and single cells of melanocytes demonstrated upward spread (melanoma in situ)
  
  • pagitoid spread when going up through epidermis

Question 61

Melanoma-Histo 2/3

Answer 61

Atypical (with no space between them) appearing melanocytes arranged in nests with many mitotic figures and dark red nucleoli.

Question 62

Melanoma-Histo 3/3

Answer 62

• Predominate melanoma in situ in which malignant melanocytes are filling the epidermis and demonstrating upward “pagetoid” growth pattern.
  
  • *upward spread of melanocytes
• melanophages are NOT pigment cells

Question 63

Melanoma In-situ lesions-gross

Answer 63

often produce pigments

Question 64

Melanoma Pathogenesis

Answer 64

• 2 most important predisposing factors: inherited genes (familial) and sun exposure
  
  • Relationship to sun not straight forward
• 10-15% of melanomas are familial
  
  • 40% CDKN2A mutations leads to loss of p16/INK4a
• Sporadic forms (de novo)
  
  • Also p16, increases in RAS and PI-3K/AKT signaling, ***BRAF*** mutations (60%), CKIT (non-sun exposed)
  • ***BRAF V600E mutations tested for
    
    • tx with vemurfenib (ZELBORAF)[anti-BRAF]**.

Question 65

Staging of Melanoma and Survival Rates

Answer 65

• Stage 0: MIS (melanoma in situ)
• Stage I/II: Confined to skin with any depth
  
  • 5 year survival 79% and 34% respectively
• Stage III: nodal involvement
  
  • 5 year survival 30-70%
• Stage IV: Distant skin or visceral metastasis
  
  • 5 year survival 9-19%

Question 66

Sample Question: The biopsy is taken from a pigmented lesion on the upper back of a 48 year old female patient. The histology shows an intradermal and dermal proliferation of nested and single melanocytes. The epidermal population of melanocytes extends well past the dermal population. There is an increase in the number of single melanocytes normally seen in the rete and many of the nests are touching forming bridges**. Many of the melanocytes appear slightly larger and demonstrate **mild atypia. The best diagnosis is:

Answer 66

compound dysplastic nevus

Question 67

Fibroepithelial Polyp/skin tag/Achrochordan (benign epidermal neoplasm) AND Epidermal Inclusion Cyst/Wen (dermal neoplasm)

Answer 67

2-for-1 special

Question 68

Follicular Neoplasm-Epidermal Inclusion Cyst (EIC)

Answer 68

• epithelium lined with granular layer
• keratin debris

Question 69

Follicular Neoplasm-Trichelemmoma

Answer 69

• cutaneous, on face
• Multiple flesh colored papules
• ***PTEN Mutations = Cowden’s Syndrome, AD
• Increase risk for breast, endometrial, thyroid ca
• follicular based from epidermis to the dermis

Question 70

Histiocytic Neoplasm-Dermatofibroma (DF); Gross

Answer 70

• Pink – brown papule or nodule most common on lower extremities
• DF “dimple sign:” Compressing the skin around the DF causes the nodule to “dimple” inward
• secondary to bug bite or trauma in the area

Question 71

Histiocytic Neoplasm-Dermatofibroma (DF)-Histo 1/3

Answer 71

• Scattered boomer-rang shaped cells of varying degree of cellularity with infiltration of the surrounding collagen at the border “trapping”
• Hyperpigmented basal layer that “tables” (flattened rete ridges)

Question 72

Histiocytic Neoplasm-Dermatofibroma (DF)-Histo 2/3 HDa

Answer 72

• Scattered boomer-rang shaped cells of varying degree of cellularity with infiltration of the surrounding collagen at the border “trapping”
• Hyperpigmented (increased melanocytes) basal layer that “tables” (elongated but flattened rete ridges)

Question 73

Histiocytic Neoplasm-Dermatofibroma (DF)-Histo 3/3 HDb

Answer 73

• Scattered boomer-rang shaped cells of varying degree of cellularity with infiltration of the surrounding collagen at the border “trapping”
• Hyperpigmented basal layer that “tables” (flattened rete ridges)

Question 74

Histiocytic Neoplasm-Dermatofibroma Sarcoma protuberans (DFSP)

Answer 74

• most commonly seen on youngish patients on the trunk.
• CP: papules or nodules (often muti-nodular) ; large nodule with multiple rotuberance
• DFSP is an uncommon cutaneous soft tissue neoplasm characterized by a slow, infiltrative growth pattern.
• considerable morbidity because of its aggressive local invasiveness.
  
  • goes deep into adipose tissue, need major sx/grafting
• Histopathological features:
  
  • Monomorphic spindle cells arranged in a “storiform”(irregularly whorled pattern) or “cartwheel” pattern.
  • dense proliferation of spindle cells in dermis
  • ***CD 34 positive

Question 75

Histiocytic Neoplasm-Keloid Scar

Answer 75

• rxn (like dermatofibroma) to trauma, often ears
• large fat collagen bundles
• (Nodular fibroblastic proliferation and the presence of hypocellular, glassy, eosinophilic, hyalinized and disordered collagen fibers in dermis.)

Question 76

What are the (3) adnexal neoplasms?

Answer 76

• often benign, but can be malignant
• Trichelemomma-follicular neoplasm
• cylindroma-eccrine/apocrine neoplasm
• sebaceous adenoma-sebaceous neoplasm

Question 77

Eccrine/Apocrine Neopasms-Cylindroma (adnexal)

Answer 77

• adnexal tumor, from glands of skin (apocrine)
• “turbin tumor” around head/forehead
• basoloid islands in puzzle pieces
  
  • compare and ocntrast to BCC:
    
    • no retraction artifact
    • different clefting
    • pink cylinders here!!

Question 78

Sebaceous adenoma-Gross + General

Answer 78

• also an adnexal!
• overgrowth of sebaceous gland
• Clinical: papule or small nodule. Yellowish. May be part of Lynch Syndrome / Muir Torre syndrome (MLH1, MSH2, MSH6) especially if multiple or cystic lesions
  • most common-face; anywhere else-do Lynch workup

Question 79

Sebaceous adenoma

Answer 79

• individual lobules where >50% of the lobule contains mature sebaceous cells.
• On the rim there will be increase in thickness of the basal cells of the sebaceous glands

Question 80

Pyogenic Granuloma-Capillary Hemangioma (Vascular Neoplasm)

Answer 80

• looks like granulation tissue (hence the granuloma)
• dermal proliferation of vessels
• epidermal cuff surrounds dermal proliferation of vessels
• lobular capillary proliferation
• mixed inflammatory infiltrate
• often ulcerated and crusted

Question 81

Leiomyoma-(pilar) smooth muscle neoplasm

Answer 81

• smooth muscle cells known for having bubbles, some cigar cells, if in a different plane
• small fascicles of bland, eosinophilic spindle cells in mid dermis (resembles arrector pili - smooth muscle of hair erection)

Question 82

What are the (4) subcutaneous diseases/neoplasms and their (2) divisions

Answer 82

• Panniculitis
  
  • Erythema Induratum / Polyarteritus nodosum
  • Eyrthema nodosum
• Tumors
  
  • Lipoma
  • Leimyoma

Question 83

Polyarteritis Nodosum (PAN)/Erythema Induratum-Panniculitis (subq)

Answer 83

• Rare, inflammatory dz (vasculitis) of small and medium sized muscular arteries
• Multiple organs; also cutaneous only variant involving small-med art. of subcutis
• Presents as palpable purpura in the skin +/- ulceration often lower limbs
• Histopathology: Inflammation of arteries in the subcutis with fibrin deposition.
  
  • there is eventual spilling out of the inflamm

Question 84

Erythema Nodosum-Panniculitis (subq)

Answer 84

• more macules (not purpuric like PAN)
• most common on front of legs
• may be associated with drugs (sulfa or NSAID or OCPs) or infections (TB) or be idiopathic
• septal fibrosis and inflammation-inflamm is in septa mostly, spills over a bit into lobules
  
  • also: Giant cells and histiocytes

Question 85

Inflammatory Dermatosis (**epidermis**)-6 main classes

Answer 85

• Lichenoid dermatitis
  
  • Lichen planus
  • Lupus erythematosis
  • Lichen sclerosis
  • Erythema multiforme
  • SJS/TENS spectrum
• Psoriasiform Dermatitis
  
  • Psoriasis
  • Lichen Simplex Chronicus
• Spongiotic Dermatitis
  
  • Acute eczematous dermatitis
• Neutrophilic / Vascular dermatitis
  
  • Leukocytoclastic vasculitis
• Granulomatous Dermatitis
  
  • Sarcoidosis
• Bullous Dermatitis
  
  • Pemphigus Vulgaris and Foliaceus
  • Bullous Pemphigoid
  • Dermatitis Herpetiformis

Question 86

Lichenoid Dermatitis-Overview

Answer 86

• band-like infiltrative lymphocytes focally kissy epidermis
• can cause basal vascular change-some edema in basal keratinocytes
• WHO??…..
• Lichen Planus**
• Erythema Multiforme
• SJS/TENS
• Lupus erythematosus
  
  • Acute lupus erythematosus
  • Subacute cutaneous lupus erythematosus
  • Discoid lupus erythematosus
• Lichen Sclerosis et Atrophicus
• Dermatomyositis

Question 87

Lichenoid dermatitis-Lichen planus***

Answer 87

• commonly located on the forearms
• 6 Ps = Pruritic, purple, polygonal, papules / plaques
• Wickham striate
• Oral involvement common
• Histopathology: lichenoid lymphocytic infiltrate with epidermal hyperplasia, wedge-shaped HYPERgranulosis, sawtoothing

Question 88

Lichenoid dermatitis-Lichen planus*** (Histo) [inflammatory “dermatitis”]

Answer 88

• High power of lichenoid dermatitis showing ***colloid bodies (CB)*** and lymphocytic infiltrate surrounding rete ridges.
• CB-died, leave apoptotic looking material
• basal-vascular changes, keratinocytes surrounded by edema

Question 89

Erythema Multiforme (EM) +SJS/TEN (Toxic epidermal necrolysis)

Answer 89

• Lichenoid dermatitis with necrotic keratinocytes (**civatte bodies**) prominent or confluent (full thickness)
• EM: self resolving caused by infections most common HSV
• SJS /TENs spectrum: drug induced, defined by mucosal involvement and ***body surface involvement*** (percentage can change) with TEN designated at >30%.
  
  • tx like they have severe burns
• Histo: EM and early SJS/TENS spectrum the lichenoid infiltrate is usually more sparse than LP (lichen planus) and the necrotic keratiocytes are plentiful and high in the epidermis.

Question 90

**Erythema Multiforme-Lichenoid (inflammatory) dermatitis**-Gross

Answer 90

• EM=anular targeted rash
• resolved spontaneously
• associated with viruses
• subepidermal blister, with necrotic keratinocytes at all levels of the epidermis.
• Clinically is a targetoid lesion with a pale/dusky center

Question 91

SJS/TEN-Lichenoid (inflammatory) dermatitis-Gross

Answer 91

widespread sloughing and oral mucosal involvement

Question 92

TEN (Toxic epidermal necrolysis)-HistoNecrotic keratinocytes at all levels of epidermis = full thickness necrosis

Answer 92

• Necrotic keratinocytes at all levels of epidermis = full thickness necrosis
• can also see the dermal splits

Question 93

Lupus Erythematosus-Lichenoid (inflammatory) dermatitis

Answer 93

• predominant cutaneous, pts dont necessarily have the serologic markers
• 10% DLE will have crossover with SLE thus have usual serologic or theyll develop it later
• Discoid LE (DLE): epidermal atrophy w/interface, superficial and deep perivascular & periadnexal infiltrate of lymphocytes with plasma cells
  
  • Dermal mucin (highlight with Alcian blue or colloidal Fe), BM thickening
• Subacute cutaneous LE (SCLE) and systemic LE (SLE): similar to DLE, but milder infiltrate, more vacuolar change; apoptotic cells more prominent in SCLE
• DIF: positive “lupus band test”, deposition of IgG, IgA, IgM, ± C3 along basement membrane
• lesions can be localized or general

Question 94

Discoid Lupus Erythematosus

Answer 94

Question 95

DLE-with PAS stain

Answer 95

use PAS stain to look at thickened membrane

Question 96

Dermatomyositis (DM)-Lichenoid (inflammatory) dermatitis

Answer 96

• Histologic findings similar to LE, but often milder with epidermal atrophy and less inflam infiltrates, no deep or periadnexal infiltrates, less mucin
• clearing of cells on basal layer, few deep
• CP: (doc in PCM)
  
  • proximal symmetrical muscle weakness
  • periorbital edema with heliotrope discoloration
  • Gottron’s papules/Gottron’s sign on the distal fingertips
  • periungal telangiectasia
  • cuticular dystrophy.
  • Violaceous erythema in shawl or photodistribution hyperkeratosis/scale over palms and soles
  • psoriasiform scalp dermatitis.
• diagnose clinically with:
  
  • elevated muscle enzymes
  • muscle biopsy with evidence of inflammation or perifascicular atrophy
  • thorough H&P

Question 97

Lichen Sclerosus et Atrophicus (LS&A)

Answer 97

• Atrophy and papillary dermal edema with collagen sclerosis, follicular plugging
• CP: whitish macule described “cigarette paper lesion” most common on the genitalia.
• Histo: first presents as a lichenoid dermatitis. The lichenoid infiltrate gets “pushed down” leaving pink hyalized collagen material behind in its place
• more cncern in older pts

Question 98

Psoriasiform (inflamm) Dermatitis-General and Gross

Answer 98

• epidermal acanthosis, thickened throughout
• inflammatory disorder of the skin-activated T-lymphocytes release cytokines, leading to proliferation of keratinocytes
• 1-2% of people in United States affected (onset: 30s)
• Associated with arthritis, myopathy, enteropathy, spondylitic joint disease, acquired immunodeficiency
• Genetic and environmental factors:
  
  • 2/3 affected have **HLA-C** ; but only 10% of HLA-C people have psoriasis
  • ***CD4+ and CD8+ sensitized cells accumulate in epidermis, antigen still unknown.
• ***Well demarcated plaques with adherent silvery white scales***
  
  • Elbows, knees, scalp, lumbosacral, intergluteal cleft and glans penis.
• 30% have nail changes
  
  • Yellow-brown discoloration with pitting
  • Onycholysis

Question 99

Psoriasiform (inflamm) Dermatitis-Histology

Answer 99

• Psoriasiform hyperplasia with parakeratotic “wafer-like” scale containing neutrophils.
  
  • Munroe microabscesses = stratum corneum
  • Spongiform pustules = intraepidermal
• Thinning of the suprapapillary plates with dilated papillary blood vessels.
  
  • ***Auspitz sign***-little pinpoints of bleeding upon scale removal
• Frequent loss of the granular layer and increased epidermal mitotic figures
  
  • eccythosis vulgaris also has this loss of granular layer-AD, acquired form

Question 100

Spongiotic Dermatitis (Inflammatory “dermatosis”)

Answer 100

• general category of dermatitis including allergic contact and atopic dermatitis (eczema)
• Histo for all: edema between keratinocytes, creating vesicle formation or space out keratinocytes
• some superficial inflammation infiltrates as well as eosinophils

Question 101

Spongiotic dermatitis-Allergic contact dermatitis

Answer 101

• Inflammatory disorder initiated by contact with an allergen to which a person has been previously sensitized
• Gross: Erythematous papules, small vesicles, or weeping plaques, which are usually pruritic
  
  • *glove-like (or shoe-like) distribution
• Usually occurs 12-48 hrs after exposure to allergen (delayed, cell-mediated, Type IV hypersensitivity reaction)
• Many plants are causes of allergic contact dermatitis: poison ivy!

Question 102

(Vesicle) Bullous Dermatitis

Answer 102

• Vesicles or bullae at any level of epidermis
• Diagnosis depends on assessment of three features:
  
  • Anatomic level of Split
    
    • could be subcorneal, intraepidermal, or subepidermal
  • Underlying mechanism responsible for split
  • Nature of inflammatory infiltrate
• Direct immunofluorescence (DIF)
  
  • Demonstrates presence of autoantibodies in the epidermis of patient skin biopsy
  • IgG, IgA, IgM, C3 most commonly used

Question 103

(Vesicle) Bullous Dermatitis-Bullous Pemphigoid**

Answer 103

• Older indivs have tense bullae
• location: Inner aspects of thighs, flexor surfaces of forearms, axillae, groin, and lower abdomen
• **Subepidermal blister/seperation with eosinophils.** (middle pic)
  
  • ​presents in a linear fashion
• IgG Ab to hemidesmonsomes where bullous pemphigoid antigen resides. The two Ag:
  
  • BPAG1: 230-kD
  • (pathogenic Ag) BPAG2: 180-kD = collagen XVIII

Question 104

Pemphigus Vulgaris-Bullous Dermatitis

Answer 104

• Most common type of pemphigus
• CP: Superficial vesicles and thin-walled bullae that rupture easily, leaving shallow, crusted erosions
• Histopath: (suprabasilar) acantholysis results in suprabasalar clefting = tombstoning.
  
  • Dissolution due to IgG antibodies against desmogleins
  • Net-like IgG and C3 on direct immunofluorescence.
    
    • due to the positioning of desmosomes between keratinocytes

Question 105

(Vesicle) Bullous Dermatitis-Dermatitis Herpetiformis

Answer 105

• most commonly found on forearm, very itchy
• Pruritic papules / vesicles on erythematous base
• Assoc w/ celiac disease
  
  • Ab to gliadin
  • ​both the vesicular dermatitis and the enteropathy respond to a gluten-free diet
• Granular IgA deposits in dermal papillae on direct immunofluorescence.

Question 106

Granulomatous (Inflammatory) Dermatitis

Answer 106

• prototype=sarcoidosis (affects lungs); presence of chronic granulomatous inflamm within the skin

Question 107

Sarcoidosis-Granulomatous (inflammatory) Dermatitis

Answer 107

• naked, non-caseating granulomas (sparse lymphocytic infiltrate) located through the dermis.
• diagnosis of exclusion and must rule out infectious causes.

Question 108

Vasculopathic/Neutrophilic (Inflammatory) Dermatitis-Histo

Answer 108

• action around the vessels
• Histo: acute vasculitis-neutrophils in the wall of the vessels
  
  • also see extravasation of fibrin on H&E

Question 109

Vasculopathic/Neutrophilic (Inflammatory) Dermatitis-Gross

Answer 109

• purpura-red papules, mixed infiltrate surrounds and damages vessel which will leave fibrin band behind and RBC will come out (extravasated from vessels)

Question 110

Henoch-Schonlein Purpura-variant of leukocytoclastic vasculitis

Answer 110

• CP: non-blanchable macules
• Accompanied by arthritis, abdominal pain, and/or hematuria
• Preceded by URI, ingestion of certain foods/drugs
• Anticardiolipin Ab and neutrophil cytoplasmic Ab of IgA class
• IgA deposition in vessel wall using DIF studies

Question 111

Tumors of cellular immigrants: Cutaneous T-cell Lymphoma

Answer 111

• neoplasm of helper T-cells (CD4+) that originate in the skin
• most common: Mycosis Fungoides (see gross)
• truncal plaques or nodules
• psoriasis is on the differential

Question 112

Tumors of cellular immigrants: Cutaneous T-cell Lymphoma-Histopath

Answer 112

• Mild epidermal hyperplasia
• Papillary dermis has a band-like mononuclear cell infiltrate composed of hyperchromatic cerebriform cells with hyperchromatic cerebriform nuclei (known as mycosis cells)
• Pautrier’s microabscesses may be seen in the epidermis, which are just aggregations of atypical lymphocytes
• Dense infiltrate of atypical lymphocytes that “line up” along DEJ=soldiers!
  
  • epidermatropism-when lymphocyte wants to be by epidermis
• Pic:
  
  • Left=atypical lymphocyte soldiers along DEJ
  • middle=Pautrier’s microabscess
  • right=cerebriform nuclei

Question 113

What are the (7) main infections of the skin?

Answer 113

• Verruca Vulgaris
• Molluscum Contagiosum
• HSV
• Impetigo
• Superficial Fungal (Dermatophytosis)
• Scabies
• Common Deep fungal infections (Blasto, crypto, histo)

Question 114

Infections of the Skin-Verruca (4 types)

Answer 114

• HPV driven, transmitted by contact, breaches skin barrier
• Verruca Vulgaris (warts) – common type
  
  • hyperkeratotic dome shaped papules or nodules located most commonly on the hands
• Verruca plana – face and dorsal hands
• Verruca plantaris / palmaris
• Condyloma acuminatum (genital and peri-anal) – HPV 6,11
• Histo:
  
  • hyperkeratosis
  • hypergranulosis
  • papillomatosis
  • koilocytes: vacuolated keratinocytes with raisin-like nuclei
  • Rete ridges often slope inward at borders of lesion (arborization)

Question 115

Infections of the Skin-Molluscum Contagiosum

Answer 115

• causes: poxvirus
• location: breast and genitalia
• RF: immunocompromised pts
• Histo: Molluscum bodies (Henderson-Patterson bodies): keratinocytes contain very large intracytoplasmic inclusions that compress the nucleus and aside
  
  • crater-produced by epidermal hyperplasia

Question 116

Infections of the Skin-Herpes Virus Infection

Answer 116

• Herpes simplex virus (HSV) 1&2 and varicella zoster virus (VZV)
  
  • Both part of human herpes virus family.
  • Both dbl stranded DNA virus with similar mechanisms for infection and ability to cause both primary and reactivated (latent) infection
  • Both cause a vesicular viral exanthem
• Positive Tzanck or direct fluorescence antibody (DFA) (rapid) of the blister contents and positive by viral culture
• Histo:
  
  • 3M’s = molding, multinucleated, marginated chromatin seen in tissue or Tzanck Smear

Question 117

Infection of the Skin-Herpes Virus Infection-General

Answer 117

• HSV1/ HSV 2:
  
  • First infection often asymptomatic
  • Primary or latent infection can present as vesicle or erosions.
  • Oral = more commonly HSV 1
  • Genital = more commonly HSV 2
• Primary VZV infection = chicken pox
  
  • Vesicles on red base/papules/crusted erosions (all stages present)
  • Transmitted by respiratory secretions and cutaneous lesions (four days prior until all lesions crusted). Vaccination available
• Reactivation of infection = shingles
  
  • Focal unilateral/dermatomal distribution unless disseminated.
  • Painful/pruritic vesicle most common on trunk
  • Increased in pts >50 or immunocompromised.

Question 118

Infection of the Skin-Herpes Virus Infection-Hutchinson’s sign

Answer 118

• HZV involvement of the nose alerts the physician to the possibility of ocular involvement
• can result in vision impairment if not treated promptly.

Question 119

Infections of the Skin-Bullous Impetigo

Answer 119

• Most common cause is Staph aureus but group A beta hemolytic Streptococcus is also common
  
  • Specifically exfoliative toxins A and B from Phage II Group 71 staphylococci attack epidermis resulting in subcorneal splitting.
• Most common in children presents as flaccid blisters that collapse easy resulting in honey colored crust
• Topical treatment
  
  • Mupirocin
• Histo: Subcorneal blister with neutrophils and bacteria present
• Microbio Correlation: Gram stain of the blister contents shows gram positive cocci in clusters.

Question 120

What are the superficial fungal infections?

Answer 120

• dermatophytes (fungus that live on keratin)
• tinea versicolor
• tinea nigra
• candidiasis: intertrigo, thrush, paronychia

Question 121

Dermatophytes (fungus that live on keratin)-4 main types

Answer 121

• superficial fungal infections caused by a dermatophyte-a species of fungi belonging to genera: Microsporum, Trichophyton, and Epidermophyton=TINEA
  
  • ​dermatophytes digest and invade keratin and may infect skin, nails, hair, and general body surfaces
• Seen as hyphae on KOH prep and in corneal layer using PAS stain of tissue.
• Classified according to location of infection
  
  • tinea pedis
  • tinea cruris-genital region
  • tinea corpora-anular scaly plaque on skin
  • tinea capitis-head; cause of allopecia

Question 122

Dermatophytosis/Onychomycosis-Superficial Fungal Infection

Answer 122

• onychomycosis: dermatophyte infection of the nail plate
  
  • breakdown keratin and some of the squames
• Left: PAS stain, Right: KOH preparation-if positive will demonstrate branching septate hyphae

Question 123

Tinea Versicolor-Superficial Fungal Infection

Answer 123

• Tinea versicolor presents as macules and patches of hypo/hyperpigmentation on trunk.
• Hyphae and yeast forms can be seen on H&E

Question 124

Infections of the Skin-Scabies

Answer 124

• Location: hands or between digits
• Sarcoptes scabiei mite; female 0.4 mm
  
  • leave scabetic poop behind, very contagious
• RF: Overcrowding/poor hygiene/sexual contact
• Papulovesicular, persistent nodules, and Norwegian (crusted) forms

Question 125

Blastomycosis-Common deep fungal infection (1 of 4)

Answer 125

• endemic in Chicago
• Epidermal acanthosis, dermal necrosis and histiocytes. Broad based budding yeast forms present in tissue.
• mixed inflammation with neutrophils, giant cells

Question 126

Coccidiomycosis-common deep fungal infection (2 of 4)

Answer 126

• single, larger form filled with tiny yeast forms

Question 127

Cryptococcus Neoformans-common deep fungal infection (3 of 4)

Answer 127

• Large, intracellular or free yeast-like organisms, mucin stains thick capsule
• stain with Mucicarmine-smaller than blasto

Question 128

Histoplasma Capsulatum-common deep fungal infection (4 of 4)

Answer 128

• Small intracytoplasmic organisms with surrounding clear halo, giant cells, PAS & GMS+
• mucicarmine negative (vs. crypto which is positive)

Question 129

Dermatomyositis (Lichenoid dermatitis)-Autoimmune disorder-Pathology

Answer 129

• Cutaneous and Skeletal Muscle Pathology
  
  • Cutaneous histology almost identical to acute lupus except frequently more epidermal atrophy
  • Myositis: perivascular mononuclear cell infiltrate , tubuloreticular inclusion in endothelial cells with myofiber damage in a paraseptal or perifascicular pattern.
    
    • Some pts have auto-Ab
    • against Mi-2 (nuclear helicase) most specific but low sensitivity
    • aminoacyl tRNA synthetase (ARS) assoc with lung dz-poor prognosis
    • p155/p140 (assoc with increased risk of malignancy); paraneoplastic presentation
    • Elevated creatine kinase (CK)-muscle dz
  • 15-30% have pulm dz (most common besides muscle dz)
  • Adult and juvenile forms
  • ***Adult form may be associated with underlying cancer

Question 130

Cutaneous findings in dermatomyositis (1 of 2)

Answer 130

• Gottron’s Papules (left)
  
  • Over knuckles
  • violaceous erythema +/- scale
• Heliotrope Rash (right)
  
  • upper lid is common (sun protected site)
  • some puffiness and edema
  • violaceous (heliotrope is a purple flower)
    
    • more lavendar that typical rosatia

Question 131

Cutaneous findings in dermatomyositis (2 of 2)

Answer 131

• holster sign
• flagellate erythema
• Gottron’s papules on the knuckles
• shawl sign
• nailfold changes-thickening of cuticles

Question 132

Cutaneous Lupus-CP (1 of 2)

Answer 132

• ***Malar “butterfly” rash***
• Photosensitive—spares nasolabial folds
  
  • areas shielded from the sun
• May be transient
  
  • will occur after sun exposure, last temporarily, then fade away with tx and time
• ***Associated with systemic lupus (SLE)
  
  • positive serology (ANA, dsDNA, etc)
  • Lichenoid dermatitis marked by basal vaculolar change
  • Overlying parakeratosis/scale +/- follicular plugging
  • Increased dermal mucin

Question 133

Cutaneous Lupus-CP (2 of 2)

Answer 133

• sometimes more patchy
• subacute
• photosensitive
• violaceous erythema

Question 134

“Chronic” Discoid Lupus erythematosus

Answer 134

• **Scarring depressed plaques (top left)
  
  • Head and neck, ears (conchal bowls*)
  • Scarring alopecia
  • Central hypopigmentation
  • Peripheral hyperpigmentation
  • skin looks shiny-indicative of scarring
• Perifollicular lichenoid dermatitis with vacuolar interface change
  
  • Mucin deposition (lots of involvement around hair follicles)
  • Thickened basement membrane.
• Most pts do NOT have systemic lupus (serology negative)-esepcially if cutaneous, limited to head and neck
• Positive direct immunofluorescence for IgG, IgM, C3

Question 135

Nailfold changes in lupus

Answer 135

• Periungual erythema
• Ragged cuticles
• Capillary loop drop-out
• ***Knuckles are classically spared (opposite of DM)-occurs between the joints

Question 136

Systemic sclerosis

Answer 136

• Scleroderma
• “Bound-down”-to deeper structures, cant pull it up
• Sclerodactyly-distal to proximal (starts and hands and feet)
• Decreased oral aperture-cant open mouth as wide
• May affect other organ systems-mostly lung, heart, GI
• 75% Female

Question 137

Limited Scleroderma

Answer 137

• “CREST”
  
  • Calcinosis cutis
  • Raynaud’s
  • Esophageal dysmotility
  • Sclerodactyly
  • Telangiectasias (spot on ring finger)
• anti-centromere Ab
• More benign course than progressive systemic sclerosis

Question 138

Calcinosis cutis

Answer 138

• hard, white-ish yellow-ish nodules-little rocks in the ermis, very difficult to tx

Question 139

Raynaud’s

Answer 139

• “Disease”stands alone
  
  • 5-10% of healthy women
  • 90% idiopathic
  • 8:1 female:male
• “Phenomenon” associated with connective tissue disease
  
  • ​**extremely common in SLE pts; cardinal feature of scleroderma
• Cold sensitivity
• episodic vasospasm of small vessels with pain (due to ischemia) and color change
  
  • white, then becomes cyanotic/blue, then hyperemic/red
• Tx with warming (especially core), avoid vasoconstrictors (worsened by beta-blockers)

Question 140

Lichen Sclerosus

Answer 140

• Often associated with localized scleroderma (morphea)
• White atrophic plaques
  
  • bound-down plaques
  • hypopigmented
  • more proximal, rarely digits
• Genital or extragenital
• Sites of trauma
  
  • Ex: injury or radiation

Question 141

Sarcoidosis

Answer 141

• “great mimicker”
• anular, pink-brown non-scaly, indurated plaque, expect nml epidermis
  
  • also: erythema nodosum, ill-defined nodules
• Non-caseating granulomas
• Often in scars/sites of trauma
• Elevated ACE levels
• May be systemic:
  
  • Pulmonary (90%)
  • Cardiac

Question 142

Necrobiosis Lipoidica

Answer 142

• Associated with diabetes in 14-65%
• Pre-tibia most common
• Atrophic yellow-pink plaques with violaceous border
  
  • can see blood vessels underneath, very shiny

Question 143

Pyoderma Gangrenosum

Answer 143

• auto-inflammatory (no infection)
  
  • extremely painful
• Inflammatory ulcer with rolled, dusky violaceous border
• Associated with:
  
  • inflammatory bowel disease (crohns, UC)
  • inflammatory arthritis
  • hematologic disorders (espeically on the hand)
• ***Pathergy-minimal trauma (or local debriment) can induce or worsen dz

Question 144

Calciphylaxis

Answer 144

• Retiform “stellate” (jagged) purpura on fatty areas
  
  • stellate-affecting the vessels (medium-sized), see that pattern of its branching
• Central black eschar
• Path shows calcium in the vessels
• Extremely painful due to ischemia
• Patients with end stage renal disease and hemodialysis
• High mortality
• Tx: sodium thiosulfate

Question 145

Palpable (NON-blanching) Purpura (1/2)

Answer 145

• Vasculitis
• Inflammatory
• Size of lesions gives a clue to size of involved vessels
• Destruction of vessels

Question 146

Define purpura

Answer 146

• extravasation of red cells into the skin
• two types:
  
  • NON-blanching palpable purpura
  • macular non-palpable purpura

Question 147

Non-palpable purpura (2/2)

Answer 147

• Vasculopathy
• Non-inflammatory
• Size of lesions gives a clue to size of involved vessels
• Thrombo-embolic
  
  • restiform/stellate form
  • (image is early calciphylaxis)

Question 148

Leukocytoclastic vasculitis (LCV)

Answer 148

• very small vessels high up in the skin; palpable purpura
• Type III Hypersensitivity (immune complexes)
• Small purpuric papules
• Predominantly lower legs
• +/- pruritus
• May ulcerate focally
• 50% idiopathic
• Triggers:
  
  • Drugs:
    
    • Antibiotics: esp beta-lactam
    • NSAIDS
    • Diurects
    • Any drug
  • Infections
    
    • URI, esp strep
    • Viral hepatitis
    • HIV
    • Bacterial endocarditis
  • Foods

Question 149

Venous Stasis Dermatitis

Answer 149

• v. common; NOT an infection
  
  • nml white count, no fever
• red brown plaques with edema swelling=shiny
• hot, often non-tender

Question 150

Acute Stasis Dermatitis

Answer 150

• skin stretched out, gets cracked, starts weeping
• itching, not much pain

Question 151

Varicose veins

Answer 151

Question 152

Stasis Dermatitis with Lymphedema

Answer 152

severe, chronic cases

Question 153

Atrophie Blanche

Answer 153

• stellate white depressed papules, surrounding stasis dermatitis
• common around ankles

Question 154

**Venous Ulcer**

Answer 154

• sequelae for untreated stasis
• medial lower leg=most common spot
• arterial ulcers are painful because of ischemia

Question 155

Capillary Malformation

Answer 155

• Vascular “birthmark”
• Slow-flow
• Grows in proportion to the child
• May be associated with other syndromes

Question 156

Arteriovenous Malformation

Answer 156

• Congenital vascular anomaly
• 40% apparent at birth
• Most common on the face
• May flare in puberty
• Diagnosis confirmed by ultrasound

Question 157

Viral Exanthem

Answer 157

• benign, dont scar, fade away
• Erythematous blanching macules and papules coalescing
• Most common in summer and fall

Question 158

Coxsackie (A) Virus

Answer 158

• Hand-foot-mouth disease
• Vesicles on the palms and soles
  
  • football shaped, oval
• Oral lesions
• Buttocks may be involved
• Fever and malaise prodrome (ahead of eruption)
• Usually follows a benign course (approx 3 wks)

Question 159

Parvovirus B19

Answer 159

• **Slapped cheeks
• **Followed by reticulated eruption on extremities (erythema)
• Arthralgia in 10% (more common in adults than kids)
• Winter and Spring
• *Fetal infection may cause anemia, fetal hydrops, or death
  
  • careful around pregnant women!!
• May also cause acral purpura “gloves & socks”

Question 160

Lyme Disease

Answer 160

• Erythema migrans
  
  • Annular erythema at site of tick bite
  • Occurs in 60-90% of patients with Lyme
  • Secondary lesions may occur
  • Borrelia burgdorferi
  • Tx: Doxycycline (adults) or Amoxicillin (kids)

Question 161

Urticaria (aka Hives)

Answer 161

• Pruritic edematous non-scaly plaques = “wheals”
• Swelling due to plasma leakage
• sometimes dermatographic-scratch the skin and it breaks into hives
• Peau d’orange appearance
• Transient (<24h), often annular or round
• Type 1 Hypersensitivity
• Many causes:
  
  • Allergy
  • Autoimmunity
  • Drug
  • Infection
  • Dietary pseudoallergens
  • Idiopathic (50%)
• Angioedema swelling is deeper in the dermis and subcutis or submucosal tissue
  
  • May affect mouth, bowel
  • Less red, more painful than itchy

Question 162

Urticaria Pigmentosa

Answer 162

• NOT the same thing are urticaria, path shows MAST CELLS
• red-brown papules
• lesions are NOT transient

Question 163

Allergic Contact Dermatitis

Answer 163

• this is due to a drug allergy, it is NOT the zoster form
• Look for “outside in” pattern
• Common culprits:
  
  • Topical antibiotics
  • Topical cleansers-Chlorhexadine
  • Nickel
  • Plants (poison ivy)

Question 164

Morbilliform=Exanthematous Drug Eruption

Answer 164

• Numerous pink papules coalescing over torso and proximal extremities
• DDx: “bug or drug” (looks like viral exanthem)
• 3.6 per 1000 among hospitalized patients
• Increased incidence associated with:
  
  • HIV
  • Connective tissue disease
  • Hepatitis
• OK to tx through the eruption
• Usually starts 7-10 days after initiation of the drug
  
  • May start even after discontinuation of the drug
  • Often starts in intertriginous and dependent areas
• May become erythrodermic (entire skin is red)
• No blisters
• No mucous membrane involvement

Question 165

DRESS syndrome

Answer 165

• DRESS:
  
  • Drug
    
    • Common culprits:
      
      • Aromatic Anti-convulsants
        
        • Anticonvulsant Hypersensitivity Syndrome
        • Patients MUST avoid all aromatic anticonvulsants
      • Antibiotics (minocycline)
      • Sulfonamides (sulfasalazine)
      • Allopurinol
      • Antiretrovirals (abacavir)
  • Reaction (Rash)
  • Eosinophilia
  • Systemic
  • Symptoms

Question 166

DRESS syndrome CP

Answer 166

• Fever
• Rash: morbilliform, infiltrated, or exfoliative dermatitis
• Facial swelling, lymphadenopathy
• Hematologic abnormalities
  
  • eosinophilia
  • atypical lymphocytes
• Visceral involvement
  
  • Liver, heart, kidney, lung
• Delayed onset: Symptoms usually develop 2-6 weeks after initiation of the drug
• Rare
• Mortality may be as high as 10% (liver failure)
• Must discontinue and avoid the offending drug

Question 167

Fixed Drug Rxn

Answer 167

• Lesions appear 1-2 wks after exposure
• With subsequent exposure, they appear within 24 hrs in the same “fixed” location
• Dusky, may blister
• Sulfa, NSAIDS, barbiturates, tetracyclines, carbamazepine
• Superficial and deep perivascular inflammation with necrotic keratinocytes

Question 168

Erythema Multiforme

Answer 168

• Targetoid lesions
• 90% Infectious causes (HSV, mycoplasma, etc)
• <10% Drugs (NSAIDS, sulfa, antiepileptics, antibiotics)
• Does not progress to TEN!
• EM Minor: targets, extremities, face, rare mucosal, no systemic sx. HSV and other infections
• EM Major: targets + occasional bullae, extremities, face, severe mucosal invovlement, systemic sx. Mycoplasma, HSV, other infection, rarely drug

Question 169

Stevens-Johnson Syndrome (SJS)

Answer 169

• Dusky macules +/- epidermal detachment
• Macular atypical targets
• <10% detachment
• Trunk, face
• Severe mucosal involvement (right)
• Systemic symptoms
• May progress to TEN
• Drugs are usually causative

Question 170

Stevens-Johnson Syndrome—Toxic Epidermal Necrolysis (SJS-TEN)

Answer 170

• Epidermolytic lesions = Painful skin lesions
  
  • epidermis detached, underlying dusky erythema
• Mucous membrane involvement
• Blisters <10% (SJS), 10-30% (overlap), >30% (TEN)
• Fever/malaise/systemic symptoms
• Stinging eyes
• Dysphagia
• Usually <8 weeks exposure to the drug
• Average mortality 1-5% (SJS) to 25-35% (TEN)

Question 171

Toxic Epidermal Necrolysis (TEN)

Answer 171

• >30% Epidermolytic lesions
• Dusky erythema
• Painful skin

Question 172

What are the causes of SJS-TEN?

Answer 172

• **Allopurinol (50%)
• Anti-convulsants
• NSAIDS
• Anti-retrovirals
• Antibiotics
  
  • TMP-SMX (Bactrim)
  • Sulfonamides
  • Aminopenicillins
  • Cephalosporins
  • Quinolones
  • Chlormezanone

Question 173

Sun Protection

Answer 173

• **BROAD-SPECTRUM UVA/UVB sunscreen
  
  • physical blockers: titanium dioxide, zinc oxide
  • chemical sunscreens: Parsol 1789, oxybenzone, Mexoryl, helioplex, antihelios
• UV Radiation: UVA (tan) and UVB (burn) contribute to premature skin aging and skin cancer
  
  • necessary to block both!!
• SPF: sunburn protection factor
  
  • measures only UVB protection
  • recommend SPF 30+
  • 1 oz (“golf ball size”) each application
  • apply every 1.5-2hr
  • water resistant=40 min
  • v. water resistant=80 min