Dermatology Flashcards
Macule
< 1 cm, non-palpable
Ex: petechiae
Patch
> 1 cm, non-palpable Ex: fixed drug eruption, - annular scaly erythematous patch of tinea, - subacute lupus - melanoma
Papule
< 1 cm, circumscribed solid/cystic elevation which can be follicular or non-follicular
- Follicular:
- Equidistant: Fox-Fodyce disease
- Ostia
- Flat-topped papules of lichen
- Verruca vulgaris
- Seborrheic keratosis
- Umbilicated of molluscum contagiosum - Pustule: light head on top
Plaque
> 1 cm
Mesa-like elevation
- Papules may coalesce to form plaque
Ex: psoriasis, eczema
Nodule
1-2 cm: solid or cystic elevation
- Extensive involvement of the dermis
Tumor
2+ cm: solid or cystic elevation
- Extensive involvement of the dermis
Vesicle
< 1 cm: usually tense
Ex: herptiform vesicles (Herpes Zoster)
Bullae
> 1 cm: may be tense or loose collection of fluid
Ex: Bullous pemphigoid
- Bullous Herpes Zoster
Erosion
Partial loss of epidermis
- Does not bleed
- All blisters, whether vesicles or bullae, eventually form ulcers or erosions
Ex: bullous impetigo (typically staph-mediated exfoliatoxin)
- Pemphigus follaceous
Ulcer
Complete loss of epidermis
- Often bleeds
- All blisters, whether vesicles or bullae, eventually form ulcers or erosions
- Accompanied by fibrin deposition
Ex: shallow ulcerations in Herpes Zoster
- Calciphylaxis (high mortality, seen in dialysis patients)
- Pyoderma gangrenosum (gun-metal gray border)
Depression
Formed when there is atrophy of subcutis
Ex: too much cortisone or anabolic steroids injected into skin (often iatrogenic)
- Lupus profundus (panniculitis)- loss of fat under skin)
Color of skin
Red: dilation of vessels modified by density of erythrocytes and inflammatory cells, melanin in epidermis, altered epidermis
Yellow: exogenous pigment, carotene, bile, lipids, solar elastosis, mast cells, altered collagen
Blue: melanin in reticular dermis
Brown/black: hemosiderin, melanin
White: loss of melanin or melanocytes or both
Burrow
Linear, serpiginous lesions of skin
- Formed when tunnel is formed in epidermis
Ex: scabies
Cord
Linear/serpiginous lesion of skin
- Formed when pathologic process involves linear/elongated structure
Ex: thromophlebitis
Risk factors for Melanoma
Familial melanoma: B-K mole syndrome
- Giant congenital nevus > 20 cm
- Bathing trunk nevus
UV radiation: intermittent blistering sunburns early in life
Atypical/dysplastic nevus syndrome patients with multiple clark/dysplastic/atypical nevi
Hereditary Melanoma
VERY rare (< 1% of all melanomas)
Germline mutations
- CDKN2A (p16): cyclin-dependent kinase inhibitor 2A
- High association with pancreatic carcinoma (15% lifetime risk)
- Don’t necessarily need to genetically test, most revealed through pedigree
Sporadic melanoma
MUCH more common than hereditary melanoma
Somatic mutations
1. BRAF= serine/threonine kinase mediating pathway of RAS signaling
- Mutation in BRAF–> turns on growth signal
- Seen in 73-82% of melanocytic nevi
- cKit: associated with acral, mucosal melanomas
Large congenital nevi
“Bathing trunk nevi”
~10% risk of developing melanoma
Skin phototypes
1-6: 1 and 2 most at risk
Type 1: fair skin, hair, freckles
Risk factors for melanoma
UV exposure–> blistering lesions (history of multiple burns in early life)
- One blistering sunburn–> doubles risk
- Intermittent exposure hypothesis (infrequent, heavy sun exposure)
Skin phenotypes:
- light skin
- Blond/red hair
- Blue/green eyes
- Prominent freckling
Clark/dysplastic/atypical melanocytic nevi
- Larger than 5 mm with irregular borders
Family history:
- 10-15% melanoma patients have positive family history
- Younger first-degree relative ex: 40 year old brother (not 85-year old grandmother)
Diagnositc tools for melanoma
Light source, magnification, polarization (dermatoscopy)
Immunohistochemistry:
Useful adjunct to H&E diagnosis of melanoma
- Poorly differentiated tumors
- Little or no pigment
- Spindle cell tumors
- + pagetoid spread –> not clearly melanoma
Stains: MART-1 (Melan-A) - Most sensitive and specific HMB-45 S-100
Superficial spreading melanoma
Most common subtype:
- Account for 70% of all melanomas
- Diagnosed most often between the ages of 30 and 50 years
Occurs at any site, most frequently:
- Trunk of men
- Legs of women
Pathogenesis:
- Asymptomatic
- Slowly changing from months-years
- Brown to black macule with color variegation and irregular, notched borders
- Best fits the ABCD criteria
- When enters radial growth phase–> papule or nodule
- Can arise de novo or in a pre-existing nevus
Nodular melanoma
Second most common type of cutaneous melanoma:
- Accounts for 15-30% of all melanomas
- Believed to arise as a de novo vertical growth phase tumor without the pre-existing horizontal growth phase
Epi:
- Mean age of onset is 53 years
- More common in men
Appearance:
- Occurs most frequently on the trunk
- Blue to black, or pink to red-colored, nodule
+/- ulceration
- Tend to be diagnosed at a thicker, more advanced stage with an associated poorer prognosis
Lentigo maligna melanoma
Represents up to 15% of cutaneous melanomas
- Diagnosed most frequently in the 7th-8th decade of life
- Arises in a precursor lesion termed lentigo maligna
- 5% of lentigo malignas progress to invasive melanoma
Pathogenesis: cumulative sun exposure
- Found on chronically sun-damaged skin
- Head and neck
- Preference for the nose and cheek
- Slow growing
Appearance: Ill-defined, asymmetric, brown to black macule with color variegation and an irregular border
- Both LM and LMM more difficult to excise because of ill-defined margins
Least association with nevi
Acral Lentiginous melanoma
5-10% of all melanomas:
- Most common subtype in darker-pigmented individuals
- 60-72% in African Americans
- 29-46% in Asians
Median age of onset being 65 years old
- Most common site is the sole
- Not all palmar or plantar melanomas are ALMs (minority are SSMs or NMs)
Appearance:
- Variegation in color and irregular borders
- May be mistaken for plantar wart or hematoma
More advanced lesion upon diagnosis associated with poorer outcomes
** ALM is not thought to be associated with sun exposure
Subungual melanoma
Variant of ALM:
- Generally arises from the nail matrix
- Most commonly on the great toe or thumb
- A widening, dark, or irregularly pigmented longitudinal nail streak (melanonychia striata)
+/- Nail dystrophy
Hutchinson sign=
- Pigmentation of the proximal nail fold
- Poor prognosis, associated with advanced subungual melanoma
ABCDE of melanoma
A: Asymmetry – one half is not identical to the other half
B: Border – irregular, notched, scalloped, ill-defined
C: Color – Varying shades from one area to the next
D: Diameter – > 6 mm or pencil eraser
E: Evolving
- Other reasons for changes in mole:
- Inflammation
- Folliculitis
- Trauma
- Hormonal influence
- Natural evolution
Histopathology of melanoma
Cytologic atypia:
- Cellular enlargement
- Nuclear enlargement
- Nuclear pleomorphism
- Hyperchromasia of nuclei
- Nucleolar variability
- Mitoses
Architectural disorder:
- Asymmetry
- Poor circumscription
- Variation in size of nests of melanocytes in the lower epidermis and dermis
- Lack of maturation of nests with descent into the dermis
- Pagetoid spread
Desmoplastic melanoma
AKA Neurotropic melanoma
Indurated papule, plaque, nodule
Pigmentation absent in at least 40% of cases (i.e. amelanotic)
Typical locations:
- Head and neck (53.2%)
- Extremities (26.2%)
- Trunk (20.6%)
Mean age 63 years old
Diagnosis is delayed due to non-specific clinical features
Histopathologically, it may simulate fibrosis/scar or a neural neoplasm leading to misdiagnosis and inappropriate treatment
Amelanotic melanoma
Pink/skin colored raised bump- harder to ID as nevi
Prognostic factors of melanoma
Most important= Breslow thickness
- Measured from the granular cell layer to the deepest penetration of the neoplasm
- Survival decreases with increasing tumor thickness
Melanoma ulceration
- Marker for aggressive nature of lesion
- Nodular lesions
- Up stage equivalent to one T level
Mitosis
- New prognostic factor as of 2009
- Proliferation of the primary melanoma
- Threshold considered significant is greater than 1 mitosis per mm2
- Adversely influences survival
- Melanoma measuring < 1mm in thickness
Anatomic site
- Worse prognosis: Head and neck, Trunk, Hand and feet; Five-year survival 84%
- Better prognosis: Arms and legs; Five-year survival 93%
Age
- Increasing age–> decreasing survival
- Patients older than 50 years of age have a 84% five-year survival vs. 90% for younger patients
Gender
- Female patients have a better survival
- Female five-year survival 90%
- Men five-year survival 83%
Prognostic factors in regional metastases
Status of regional lymph nodes most powerful prognostic factor for survival
- Presence of regional lymph nodes portends a worse prognosis
- Number of lymph nodes involved is the most significant risk factor
The second most important risk factor is tumor burden
- Micrometastatic disease (SLN Bx) vs. macrometastatic disease (clinically palpable disease)
Worse prognosis:
- Ulceration
- Satellites
- Both clinical and microscopic metastasis around a primary melanoma
- In-transit metastasis: Intralymphatic metastases between the primary tumor and its nodal basin
Prognostic factors in distant metastases
Site of metastasis – most important factor
- Visceral metastases poorer prognosis than non-visceral (skin, subcutaneous tissue, distant lymph nodes) sites
- Number of metastases
- Amenable to surgical resection
Psoraisis Vulgaris
Pathophys:
- Multifactorial disorder with genetic predisposition
- New immune cell recognised: TH17 cell–> increased IL 17 causing increased keratinocyte proliferation–> chemokine release–> skin defense
Risk factors:
- Strep pharyngitis
- Stress
- Skin trauma (scratches): Koebner phenomenon
Features:
- Nail pitting (v. difficult to treat)- increased risk of psoriatic arthritis
- Morning stiffness
Psoriasis Inversa
Skin fold regions (inverse of expected region)
Does not have silver plaques
Erythroderma
Defined by erythema and desquamation involving more than 90% of skin surface
Differential:
- Skin eruption
- Infection
- Allergic reaction
Pustular psoriasis
May be systemically ill
- Need to be followed/assesed for: hypocalcemia, hypotension, fever
Care must be given with systemic steroids as taper–> pustular flare
Psoraisis treatment
Local:
- Corticosteroids
- Vit D analogues
- Tar
Phototherapy:
- PUVA
- Narrowband UVB
Systemic:
- Retinoids (push cell differentiation)
- Methotrexate
- Cyclosporine
- Mycophenolate mofetil
- TNF-alpha inhibitors for psoriatic arthritis
Atopic dermatitis
3/4 major features:
- Prutitus
- Typical morphology and distribution
- Chronically relapsing
- Personal or family history of atopy
Usually not before 3 months of age
- Relies on patient sratching it
In infancy:
- face= common site
- sites where they can rub against bed, reach easily
- May see failure to thrive
Childhood/adulthood
- Flexural surfaces= common sites
- Chronic involvement can lead to lichenification (skin thickens)
Features:
- White dermatographism (not red wheal, but white wheal)
Theory behind pathophys:
- Immunologic abnormalities (humoral immue, t-cell mediated immune response)
- Structure of skin abnormal (BAD skin)
- Defect in humoral immune response: high levels of serum IgE, binding to langerhaans cells
- Antigen-induced activation of IgE-bearing cells (mast cells, macrophages)
- Decrease in cyclic AMP–> hyperreactive mast cells, Langerhans’ cells
Exacerbating factors:
- Anxiety, stress
- Climatic factors: temps, humidity
- Irritants: detergents, solvents, wool/rough material
- Food, contact, inhaled antigens
Itch-scratch cycle
Pruritis precedes visible eruption
- C-fibers transmit itch first
Scratching–> increased release of histamine from mast cells–> pruritis
Differential diagnosis of Atopic dermatitis
Differential diagnosis:
- Psoraisis, scabies, eczema
- Wiskott-Aldrich (eczema, thrombocytopenia, immunodeficiency)
- Hyper-IgE (cold staph abscesses- not painful/hot, eczema-like rashes, lung infections)
- Cutaneous T-cell lymphoma
Seborrheic Dermatitis
Earlier onset=typical
Absent pruritis
Limited distribution on face, groin
- Greasy scaly macules and patches on the central part of the face (nose, mouth, and eyebrows).
- Scalp is a common site of involvement, which the patients complain of bad “dandruff.” The condition is seen in neonates (e.g. cradle cap), which resolves when the maternal hormones are washed out.
- The condition is usually not seen in prepubescent age. In adults, the condition is more common in patients with neurologic diseases such as Parkinson’s disease.
Cause: belief that condition is caused by a commensal fungus, namely, Malesezzia furur.
Treatment: antifungal creams and shampoos are often recommended such as ketoconazole cream and shampoo. Other treatments include zinc based soaps and shampoos, immunomodulators such as pimecrolimus, and low potency steroid.
Scabies
Papules, burrows, nodules
Distribution:
- Infants= generalized
- Adults: finger webs, wrists, exillae, groin
Pruritis in patient and contacts
Mite debris on microscopic examination
Eczema herpes
Disseminated Herpes Simplex Virus (HSV)
Painful umbilicated pustular vesicles
Fever, malaise, lymphadenopathy
Significant morbidity and mortality (risk of systemic herpes infection)
Seen in patients with atopic dermatitis or other chronic skin conditions:
- dissemination of the cutaneous herpes simplex virus into the eczematous skin may lead to the eruption of clusters of umbilicated pustular vesicles known as eczema herpeticum or Kaposi’s varicelliform eruption
Impetigo
Pustular vesicles with straw-colored discharge
- Due to staph aureus infection
Treatment for atopic dermatitis
- Topical steroids or immune modulators: tacrolimus, pimecrolimus
- Antihistamines
- Wet wraps
- Coal tar in ointment base, anthralin
- Antibiotics (topical, oral)
- Leukotriene antagonist
Flares:
- PUVA, UVB
- Systemic steroids
- Immunomodulators (cyclosporine, tacrolimus, azathioprine)
Lichen planus
Pruritic disorder of skin, mucous membranes
Appearance: violaceous polygonal papulaes, plaques on penis
- Hypertrophic or erosive
Oral mucosa with typical white reticulated plaque
- Associated with HCV
Erosive lichen planus= increased risk of squamous cell carcinoma in oral/mucosal lichen planus
- v. painful, can cause scarring/disfigurement
Lichen Nitidus
Variant of lichen planus
Seen in children
- non-pruritic
Acne keloidalis nuchae
Chronic folliculitis–> scarring ressembling keloids in darker-skinned individuals
Abscesses
Cause: Staph
- Furuncle= single follicle
- Carbuncle= multiple follicles
Treatment with I&D and antibiotics
- Chronic abscesses due to carriage
Hidradenitis Suppurativa
Inflammatory non-infectious process
Multi-focal and symmetric involving 2+ locations
- Treatment is difficult, scarring results
Epidermal cysts
Firm, mobile nodules
Treatment: I&D
Scarlet Fever
More common in kids, caused by Group A strep erythrogenic exotoxin
- 24-48 hours after sore throat
- Sandpaper-like papules
- Pastia lines, desquamation of palms and soles
Diagnosis: strep culture, ASO
Treatment: antibiotics
Erysipelas
Group A strep (except in post-partum/newborns= Group B strep)
- Infection of superficial dermal lymphatics from lacrations
- Erythematous, brawny plaque on face, legs
Treatment: oral antibiotics
Cellulitis
Staph or strep
Port of entry: tinea pedis in toes
Usually unilateral, can be bullous
Treatment: IV antibiotics
Stasis Dermatitis
Chronic venous stasis–> extravasated RBCs
- Erythema, yellow-brown plaques with lichenification
- Often bilateral
Treatment: compression, topical steroids
Erythema migrans
Borrelia burgdorgeri= Lyme disease
- 3-32 days after bite as papule–> annular
- 25-50% develop multiple lesions
- Fades without treatment
Treamtent (for Lyme): doxycycline
HHV 3
Varicella= Chicken pox
Herpes Zoster
HHV5
Cytomegalovirus
In adults: similar to EBV infection
In neonates: TORCH syndrome
- Blueberry muffin baby
Can also co-infect with HSV
Treatment: gangciclovir
HHV6
Roseola
- Self-limited, seen in babies
Pityriasis Rosea:
- Viral exanthem
- 20% have mild flu-like symptoms
- begins with 2-10 cm oval, scaling patch for 1 week–> followed by smaller oval patches (cigarette paper scale “christmas tree”)
- Treatment: topical steroids for itch (rash recedes on its own
- Mimicker= secondary syphillis (6-8 weeks post-chancre)
Tinea versicolor
Caused by Malasseziafurfur
- Well-demarcated hypo/hyperpigmented patches on skin
Treat: topical antifungals
Tinea corporis/captis/pedis
T. rubrum, T. Metagrophytes, M. Canis, T. tonsurans
- Annular lesions with peripheral scale
Diagnosis: KOH stain
Treatment: topical antifungals
Mimicker: seborrheic dermatitis
- More common in adults than tinea
- Pityrosporum ovale
- Greasy scale over erythematous plaques (sebaceous areas)
- More common in patients with neurologic disease
- Treatment: topical antifungals
Majocchi’s granuloma
Dermatophyte invades and ruptures hair follicle
Mimicker: nummular dermatitis
- Commonly found on extremities
- round, erythematous plaques with scale
- Spongiotic dermatitis
- Treat with topical steroids
Deep fungal infections
Subcutaneous mycoses: chromoblastomycosis
- Caused by Fonasacea pedrosoi
- Verrucous plaques, nodules
- Diagnosis: sclerotic bodies on H&E
Treatment: oral antifungals
Atypical mycobacteria
M. fortuitum, M. chelonei, M. Abscessus
- Infections linked to surgical procedures and nail salon baths
Treatment: debridement, combination antibiotics
Norwegian (crusted) scabies
Immune-compromised, debilitated patients
HUGE mite load
- Hyperkeratotic lesions
BOTH topical or oral therapy needed
Skin conditions involving subcorneal split
- Impetigo: staph, s. pyogenes
- Bullous impetigo: staph exfoliative toxin
- Staph “scalded skin” syndrome: no bacteria in skin samples
Mimicker:
- Pemphigus foliceous: auto-antibodies to desmoglein 1 (cell adhesion complex)
- Toxic epidermal necrolysis: necrosis of epidermis (deeper splitting)
HHV4
Epstein Barr virus
Can cause morbiliform eruption
7-10 days after amoxicillin/ampicillin treatment
Epidemiology of basal cell carcinoma
Most common malignant neoplasm in humans
Most common form of skin cancer, and now most common form of cancer in United States
Rarely metastasizes, but can be locally destructive
Associated with long term chronic UV exposure
75% of non-melanoma skin cancers
99% in Caucasians
Majority in patients 40 years and older but not uncommon in 20-40 year olds
85% on head, neck, and trunk
Etiology of Basal cell carcinoma
Pigmentary phenotype-Fitzpatrick I-II Ultraviolet light exposure- intense episodic Radiation exposure Pre-existing skin lesions - nevus sebaceous Genetic Syndromes - Basal cell nevus syndrome - Xeroderma pigmentosa
Clinical features of basal cell carcinoma
Nodular
- Smooth translucent, pearly papule, overlying telangiectasia +/- ulceration, pigmentation
Micronodular
- More plaque like with less defined borders
Superficial
- Erythematous or atrophic macule with raised peripheral borders
Infiltrating/Sclerosing
- Scar like plaque with ill defined borders
Basal cell nevus syndrome
Range of clinical findings include:
- Numerous BCCs (photodistribution),
- palmar pitting,
- hypertelorism,
- ondontogenic cysts,
- bifid ribs,
- brachymetacarpalism,
- calcification of falx cerebri,
- partial agenesis of corpus callosum,
- ovarian fibromas,
- medulloblastoma
Genetics:
- Transmission sporadic or autosomal dominant
- Chromosomal defect 9q p22
Treatment of basal cell carcinoma
Excision:
- Conventional (3-4mm margins)- vertical sections
- Mohs micrographic surgery- sectioned vertically and horizontally:
Destruction- ED&C, Cryotherapy
Immunomodulators-
- Topical imiquimod (Aldara™)
Radiation
- elderly, poor operative candidates, or palliation
Indications for Mohs micrographic surgery (MMS)
- Recurrent BCC
- Ill defined borders
- Cosmetically important area/Tissue sparing
- Size > 2.0cm
- Increased risk of recurrence: Location on nose, ears; infiltrating or micronodular histology
Principles:
- Excision of tumor as complete block
- Horizontal embedding technique
- Peripheral and deep margins embedded on same horizontal plane
- 100% margin evaluation
- Intraoperative histologic evaluation and mapping of residual tumor
- Additional tissue layers taken selectively until negative margins
- Allows for immediate reconstruction
Squamous cell carcinoma: epidemiology
- 20% of non melanoma skin cancers
- Uncommon but not rare in non Caucasians
- Male:Female ratio= 3:1
- Increased incidence with increasing age >40
- Occurs on areas of chronic sun exposure: Head, neck, dorsal hands
Squamous cell carcinoma: etiology
Pigmentary phenotype- Fitzpatrick I, II Ultraviolet Radiation- chronic recreational, therapeutic, PUVA Chemical carcinogens Chronic ulceration or scar (Marjolins ulcer) HPV Immunosuppression (transplant- heart 65x increased risk) Genodermatoses (XP, EDV)
Actinic keratoses
AK is precursor to SCC
- Clinically erythematous scaling macule or papule on sun damaged skin
- Can regress, remain stable, or progress to SCC
Malignant conversion rate ~ 1/200 or 1/1000 per year
- 10% risk of SCC in 10 years with 10 AKs
Treatment : liquid nitrogen, topical 5FU, imiquimod (Aldara™)
SCC- clinical features
SCC in situ (Bowen’s)
- erythematous scaling macule
SCC- invasive
- Erythematous nodule or eroded plaque
SCC/KA type (keratoacanthoma)
- Rapidly growing nodule with central keratin plug
Verrucous carcinoma
Erythoplasia of Queyrat-
- moist red plaque on genitalia
SCC- indications for MMS
High risk for recurrence, metastasis
Perineural involvement (must check patient for palsies, pain, etc) - spreads along cleavage plane between nerve and sheath (seen in 2-14% of all SCC, 1% of BCC)
Invasion into bone
Recurrence
UVR exposure and skin cancer
Skin Cancer (SCC) - Peak effect at 300nm (UVB) in mice Photoaging - Elastosis - Irregular pigmentation - Telangiectasia - Peak effect at 340nm (UVA)
Mechanisms:
- DNA Damage
- Pyrimidine dimer formation
- Activation of oncogenes or inactivation of tumor suppression genes
- Damage to two alleles leads to neoplasia - Immunologic Suppression
- Decreased immune surveillance by down regulation of Langerhans cells
- Altered cytokine production
Basal cell nevus syndrome and hedgehog pathway:
Candidate gene for BCNS localized to chromosome 9q22.3
- PTC - putative tumor suppressor gene
- Two hit hypothesis:
1. BCNS associated with inherited mutations in one allele
2. UVR produces additional defective allele leading to neoplasia
The “patched” gene=
- Tumor suppressor gene that encodes a transmembrane protein in ‘Hedgehog’ signaling pathway
- regulates cellular proliferation and organ development during embryogenesis
- Implicated in the development of sporadic BCC and other tumors: lung, prostate, pancreatic, gastric, hepatocellular, neural
Treatment:
- Cyclopamine (inhibits HH pathway)
- Steroid alkaloid and teratogen
- Foundin Rocky Mtn wildflower= Veratrum californicum - Vismodegib: FDA-approved BCC tx
p53 and skin cancer
Tumor suppressor gene on chromosome 17p13.1
- Mutations found in 50% of human cancers including skin cancer
Transcription factor for genes controlling apoptosis
- Loss of suppressor functions can lead to neoplastic proliferation
Mutations in skin cancers are pyrimidine dimers c/w UV induction
- Mutations in 60% of AKs, 90% of SCC, 50% of BCC
- P53 mutations prevent apoptosis of UV damaged cells
- Additional UVB can lead to clonal expansion, carcinogenesis
Xeroderma pigmentosa
Rare AR genodermatoses
Defective DNA endonuclease
- Inability to perform normal DNA excision repair
Clinical features:
- Severe actinic damage, early onset cutaneous neoplasia
- Cataracts, photophobia, keratitis
- May be associated with neurologic impairment (De Sanctis-Cachione syndrome)
Characteristics of UVA/UVB
UVA:
- Penetrates into epidermis/dermis
- Not filtered by glass
- Leads to dermal collagen damage
- Seen throughout day, all year
UVB:
- Absorbed in epidermis
- Erythema of sunburn
- Seen in late spring, summer, autumn, midday
Both:
- Cause photo aging
- Skin cancer (more UVB)
MED= minimal erythemal dose
Minimal erythemal dose
- Smallest dose of UV radiation that can induce sunburn
- Not necessarily correlated with skin type
Ex: Burn after 1 minute of sun exposure
- SPF 30= 30 minutes to get burned from sun exposure
Pruritic disorders: skin changes
Follicular accentuation Lichenification Post-inflammatory pigmentary alteration Excoriation Picker's nodules/ Prurigo nodularis Ulcers/erosions
Differential diagnosis of pruritis
Primary: skin diseases:
- Xerosis (dry skin, eczema craquele, senescence)
- Scabies
- Urticaria (comes and goes rapidly)
- Dermatitis herpetiformis
- Urticarial stage of bullous pemphigoid
- Contact dermatitis
Iatrogenic:
- Medication-induced pruritis
Secondary: Systemic disease
- Chronic renal disease
- Liver disease (cholestasis)
- Iron deficiency
- Polycythemia vera
- Thyroid disease
- Parasitic infestation
- Lymphoma
- Diabetes
Treatment of pruritis
No effective specific antipruritic drugs:
- Topical agents (corticosteroid, phenol, menthol, opioid)
- Oral antihistamines
- Systemic corticosteroids
- SSRIs
- UVB radiation
Venous insufficiency
Incompetent one-way bicuspid valves in veins of legs prevent backflow–> chronic inflammation, fibrosis, etc.
- With aging, valves compromised (incompetent)–> dilated veins
Seen in 6-7% population > 50 years:
- Superficial veins (most common): saphenous veins, tributaries
- Deep veins: anterior and posterior tibial, peroneal, popliteal, deep femoral, superficial femoral, iliac veins
- Perforating veins
Causes:
- Congenital, abnormal valves
- Age-related
- Trauma (injury, vein stripping)
- Venous thrombosis
Symptoms:
- Throbbing, burning, aching, heaviness, restless legs, leg fatigue
Clinical manifestations:
- Spider veins
- Varicose veins
- Stasis dermatitis (often confused with bilateral cellulitis)
- Acroangiodermatitis of Mali (tumor-like veins)
- Stasis ulcers
- Lipodermatosclerosis (loss of hair, shiny scar-like skin)
Treatment:
- Compression
- Sclerotherapy
- Vein stripping with ligation
- Valvuloplasty
Toxic epidermal necrolysis
TEN= acute widespread blistering eruption caused by drugs
Culprits:
- Antibiotics (bactrum, sulfonamides, ampicillin)
- Anticonvulsants (phenytoin)
- Allopurionol
- NSAIDs
Clinical:
- Eruption preceded by morbilliform, generalized erythema
- Nikolsky sign (blister expands with physical manipulation)
- Mucositis
- Diff diagnosis: staph scalded skin
Treatment:
- Supportive care (similar to burn pt: fever, hyperthermia, hypotension due to volume losses, tachycardia, pneumonia, sepsis)
- Corticosteroids (only if early)
- High dose IVIG
Mortality= 25-50%
Dermatitis herpetiformis
Blistering disease of skin due to immune-complex deposition in papillary dermis
- More common in N. Europeans
- Age of onset= 2nd-3rd decade
- 20% of patients have celiac disease, over 90% have GI findings on endoscopy
Clinical findings:
- Herpetiform (grouped) vesicles symmetrically distributed on knees, elbows, forearms, buttock, scalp (rare)
- May have crusted lesions with non-specific pruritis (like atopic dermatitis, scabies, drug eruption)
Pathogenesis:
- Circulating antibodies including IgA to:
- Gliadin (antigen= wheat protein)
- Reticulum
- Smooth muscle endomysium
- Tissue transglutaminase - Deposition of immune-complexes in mucosa of:
- Small intestine (malabsorption symptoms)
- Papillary dermis of skin (blistering)
Diagnosis:
- Antigens in skin:
- epidermal transglutaminase
- antigen-antibody complex deposits in skin
- NON-circulating - Skin biopsy
- lesional skin forhisto: subepidermal bulla with neutrophils
- Peri-lesional skin for immunofluorescence study (granular IgA deposition) - Tissue transglutaminase Ab in serum
- DQ2/DQ8 HLA testing
- high prevalence in normal population (low positive predictive value)
- High negative predictive value
Treatment:
- Gluten-free diet (slow improvement)
- Dapsone (anti-neutrophilic for skin symptoms)
- Monitor for enteropathy-associated T-cell lymphoma (due to constant antigenic stimulation); DQ2 homozygotes at high risk
Porphyria Cutanea Tarda
PCT= most common cause of all porphyria
2 forms:
- Sporadic (80-90%):
- Decreased activity of uroporphyrinogen decarboxylase in liver secondary to underlying liver disease - Familial (10-20%):
- Decreased activity of uroporphyrinogen decarboxylase in all tissues, including erythrocytes
* * Most gene carriers asymptomatic until sufficient liver damage occurs
Preciptiators:
- Male, over 40, alcohol
- EtOH, estrogen, hexachlorobenzene, iron overload
- Iron overload (in PCT)-_> decreased uroporphyrinogen decarboxylase activity
Pathogenesis:
- Uroporphyrinogen decarboxylase deficiency–> accumulation of photoactive molecules that absorb visible violet light
- Photo-excited porphyrins in skin–> oxidative damage–> photosensitivity reactions
Clinical manifestations:
- Photosensitivity
- Blisters and skin fragility on sun-exposed sites, dorsa of hands and feet, face
- Shiny skin
- Hypertrichosis (Hairy face)
Associated disease:
- Hep B, C
- HIV
- Beta-thal
- Hemachromatosis
- Hepatocellular carinoma
- EtOH
Diagnosis:
- Skin biopsy (pauci-inflammatory subepidermal bulla= epidermal lifting with no inflammation, necrosis)
- Fresh urine (pink to orange-red with Wood’s lamp)
- Porphyrin analysis (24 hr urine, plasma, stool)
Treatment:
- Phlebotomy (decrease Fe overload)
- Hydroxycholorquine (anti-malarial)
- Block sun exposure
Panniculitis: Erythema nodosum
Occurs at any age, generally young, healthy adult women
- Tender erythematous nodular eruption (pre-tibial)
- May be accompanied by arthralgia (ankles, knees, wrists)
- Septal panniculitis
Hypersensitivity reaction associated with other diseases, but 1/2 idiopathic
- Infections (strep, viral, fungal)
- IBD
- Drugs (OCP, sulfonamides, penicillin)
Usually self-limited
Treatment:
- Oral corticosteroids, SSKI (super-saturated potassium iodide)
Panniculitis: Necrobiosis Lipoidica
Unknown pathogenesis
Morphology:
- Plaques with violaceous brown border, atrophic center
- Histiocytes, lymphocytes, plasma cell around blood vessels
Epidemiology:
- 0.3% diabetic patients have NLD
- 22-65% with NLD have diabetes
- Avg age= 30 years
No effective treatment:
- intralesional steroids
- doxycycline (anti-granulomatous)
Leukocytoclastic vasculitis
ex: Henoch-Scholein Purpura, Behcet’s disease
Immune-complex deposition mediated destruction of post-capillary venules
Skin= most common involved organ
- Purpuric papules (palpable purpura)
- Urticarial papules, purpuric macules, vesicles/bullae, pustules, ulcers
- Distal areas, classically bilateral legs
Skin lesions my have systemic signs/symptoms:
- Fever, joint pain, abdominal pain, bloody urine
- may indicate internal organ involvement
Manifestation of diseases/meds:
- Connective tissue diseases
- Viral, bacterial infections
- Malignancies, lymphomas/leukemias
50% cases are idiopathic
Workup: CBC, BUN, Cr, LFT, ESR, RF, ANA, Antistreptolysin, cryocrit, serum protein electrophoresis, hepatitis serologies
Histo:
- Neutrophils
- Extravasated RBCs
- Fibrin deposition around vessels
Treatment: NSAIDs, antihistamines Colchicine Antibiotics (Dapsone) Corticosteroids
Henoch-Shonlein purpura
Form of LCV:
- viral or bacteria-induced
- frequently involves joint, GI tract, kidneys
- Children 3-10 years of age
- Immune complex consists of IgA (vs IgG)
High risk of ESRD:
- Serial urinalysis to detect kidney involvement (hematuria)
Polyarteritis nodosa
Necrotizing neutrophilic vasculitis of small to med-sized vessels with predilection for GI tract, liver, kidneys, skin
Symptoms:
- Fevers, arthralgia, myalgia, abdominal pain, mononeuritis multiplex, renovascular HTN, microaneurysms, NO pulmonary involvment
- Skin involved in 50% cases, livedo reticularis, plaques, nodules, ulcerations
- 10% skin-limited
Associated with:
- Hep B (7%)
- Hep C, HIV, strep, CMV, parvo B19
- Most cases idiopathic
Presentation:
- ulceration
- dispigmentation: retiform purpura on legs- worrisome vasculitis/vasculopathy (non-blanching)
- nodules
Antiphospholipid syndrome
APL syndrome seen in women (80%) ~42 years old
1-5% young, health people have Antiphospholipid antibodies without consequences
- Occur with other conditions; IgM are present at low levels (infections, cancer, drugs, hemodialysis)
Group of heterogeneous antibodies:
- Lupus anticoagulant
- dilute Russell’s viper venom time (PTT prolongation)
- Corrects with addition of excess phospholipid/platelets - Anticardiolipin
- ELISA on cardiolipin-coated platelet in presence of bovine serum - anti-beta2 glycoprotein antibodies (phospholipid binding proteins)
- ELISA for coated platelets
Diagnostic criteria:
- Anticardiolipin or lupus anticoagulant antibodies 2+ times, 6 weeks apart
- Clinical: vascular thrombosis +/- pregnancy complications
Clinical classfication:
- Primary: no associated disease (90%)
- Secondary: SLE, RA
Presentation:
- Thrombosis of large and small vessels of both arteries and veins of any organs
- deep venous thrombosis= most common
- arterial thrombosis= strokes and TIA - Complications
- pulmonary emboli
- emboli of vegetation of cardiac valves
- gynecologic: miscarriages usually during fetal period, premature delivery - Acute involvement of small vessels= similar to HUS, TTP
- results in loss of organ function
- Catastrophic antiphospholipid syndrome
Cutaneous manifestations:
- superficial thrombophlebitis
- ulcers
- livedo reticularis
- acrocyanosis
Treatment:
- High intensity warfarin therapy (INR: 3.1-4.0)
- Plasmapheresis and/or IVIG for refractory and “catastrophic” cases
Differential diagnosis for ulcers
infections malignant neoplasms vasculitis vascular insufficiency diabetic ulcers pyoderma gangrenosum calciphylaxis factitial ulcers
Work-up: Skin biopsy, swab culture, tissue culture
Pyoderma gangrenosum
Diagnosis of exclusion
Chronic suppurative inflammation resulting in tissue destruction
Size and depth of the ulcers vary
Associated diseases:
- inflammatory bowel disease, especially ulcerative colitis
- IgA monoclonal gammopathy
- leukemia
Calciphylaxis
Almost exclusively seen in patients with end-stage renal disease
- Progressive calcification of small arteries result in ischemic necrosis of the skin
- No effective treatment
- High mortality rate-60 to 80% due to sepsis
Histo: fractured blood vessel lining= calcification
Treatment: difficult (already sick with dialysis
Systemic Amyloidosis
Underlying causes: Multiple myeloma and Waldenstrom’s macroglobulinemia
- Amyloid consists of immunoglobulin light chains
- Deposition may occur in any organs
Skin and mucosal lesions
- deposits in vessels result in purpuras (leaky vessels)
- pink translucent papules and nodules
macroglossia
Classic sign: carpal tunnel syndrome and purpura (e.g. raccoon eye sign, pinch purpura)
Diagnosis:
- Skin biopsy
- amorphous pink homogeneous material
- stains with Congo red, which turns bright green fluorescence upon polarization - Rectal mucosal biopsy
- Abdominal subcutaneous fat aspirate
Eruptive Xanthoma
Usually widespread eruption of yellowish papules
- High triglcyeride level due to lipoprotein lipase deficiency, less often seen in patients with diabetes and patients on retinoids (accutaine, isotretinoins)
- Skin biopsy shows lipid laden foamy histiocytes and interstitial deposition
- Complications include pancreatitis and atherosclerosis
Mycosis fungoides
The most common form of T-cell lymphoma of the skin (NOT fungus!)
Clinical stages include patch, plaque, nodular, tumor, and erythrodermic stages
- Unlike psoriasis, which has flares and remission, this is continuous
Most patients have patches for a lifetime and a few will have progressive disease resulting in death
Pathogenesis:
- Neoplastic proliferation of T-helper cells (CD4+)
- Sézary cells (CD4+ cells with convoluted nuclei) are found in the blood in the erythrodermic stages
Treatment will depend on the clinical manifestation, but the disease is incurable
Kaposi’s sarcoma
Virally induced (HHV8) vascular hyperplasia rather than a neoplasia
- Metastatic vs multifocal
- AIDS defining disease (HHV8 infection accompanied by immune suppression to manifest)
In immunocompromised individuals, it can be found in the skin and in any visceral organs, especially:
- GI bleeding, pulmonary hemorrhage, lymph nodes
4 types:
- Epidemic AIDS related
- Usually related to low CD 4 count - Classic/ sporadic
- Elderly Mediterranean/ Eastern European men
- Seen in lower extremity
- NOT immune compromised - Immunocompromised
- Transplantation
- Sirolimus (mTOR inhibitor- can cause OR treat in transplant patients), anti-VEGF, antiangiogenesis - Endemic/ African
- Indolent or aggressive
- Lymphadenopathic form in children
Manifestations:
Patch, plaque, nodular, exophytic, infiltrative, lymphadenopathic
Histology
- Spindle cell proliferation of endothelial cells with slit-like vascular spaces, extravasated RBCs
- May be more lymphatic in origin than vascular by staining patterns
Sweet’s syndrome
Paraneoplastic syndrome (remote effect from primary neoplasm- paraneoplastic pemphigus, necrolytic migratory erythema, erythema gyratum repens)
- Acute febrile neutrophilic dermatosis
Characterized by: - tender edematous erythematous papules and plaques
- accompanied by fever and peripheral neutrophilia
Skin biopsy:
- band like infiltrate of neutrophils in the dermis with edema of the papillary dermis
- no leukocytoclasis of neutrophils (no dust)
Associated with:
- acute myeloid leukemia
- drugs-GMCSF (neutrophil maturation)
- pregnancy
- inflammatory bowel diseases
- upper respiratory infections
Treatment:
- Corticosteroids (treat infection/ malignancy first)
Acanthosis Nigracans
Velvety hyperpigmentation usually on the neck
- Most frequent association is obesity
- Rarely, association with adenocarcinoma of the GI tract has been described
Fixed drug eruption
Recurrent hyperpigmented patches with repeated use of drug
- Can also see central necrosis in patch–> bullae
Tx: stop offending agent
Common offenders: barbiturates, tetracyclines, pseudoephedrine, nsaids/naproxen, erythromycin, sulfonamides, phenolpthalein
Morbiliform drug eruption
Generalized rash maculopapular with no malaise
- Reaction to drugs started in past 2-3 weeks (unless previously exposed, could be 24-48 hours)
Tx: identify and stop offending agent, topical steroids, +/- prednisone taper
Workup: Monitor for evolution, mucosal involvement, onset ( avg =3 weeks)
- CAN treat patient with same drug again (non life-threatening reaction); sensitize patient to drug in ICU
DRESS
Drug eruption + Eosinophilia and Systemic symptoms
- Severe drug rash
Clinical:
- widespread morbilliform eruption
- oral mucosa (usually one site only)
- avg time to onset 21 days
Eosinophilia- ~50% cases
Systemic Involvement-
- elevated LFTS,
- renal insufficiency,
- hematologic abnormalities,
- fever
- LAD
HHV6 association
Common offenders: allopurinol, dapsone, phenytoin
Stevens Johnson Syndrome
Rash: erythematous macules coalescing into vesicles denuding
Pathogenesis: extensive keratinocyte death via apoptosis
Mucosal Involvement: 3 sites
Body surface area Involvement %
SJS: < 10% ;
10% < SJS/TEN 30% involvement
Treatment: Derm Consult.
- Identify and stop offending agent.
- 95% cases due to drug (NSAIDS, Antibiotics (sulfas), Anticonvulsants)
- No good treatment;
- IVIg vs IV corticosteroids early
Supportive care. Transfer to burn unit. Opthalmology consult.
Prognosis: high mortality rate: 5% (SJS), 35% (TEN)
Risk?
- AIDS- 1000x fold increase
- Slow acetylators
- Immunocompromised
- Brain tumor patients on anti-epileptics with radiation therapy
- screen for HLA-B1502 in Asian patients to be prescribed carbamazepine
Acne inducers
Even stupid drugs like hormones induce acne vulgaris:
- EGFR inhibitors,
- steroids,
- dilantin,
- lithium,
- halogens,
- INH,
- ACTH,
- Vitamins
Embryological development of skin
- Epidermis forms as single layer in first weeks of embryogenesis
- Neural crest elements (melanocytes) migrate to the epidermis (8th week)
- Adnexa (hair, eccrine glands) form around 12th week as invaginations from the epidermis into the dermis
- Sebaceous and apocrine glands sprout from follicular epithelium
Normal skin structure
Epidermis: stratum basale, spinosum, granulosum, lucidum, corneum
- keratinocytes (adnexae)
- melanocytes
- Langerhans cells
- Merkel cells (sensory)
Dermis:
- fibroblasts (elastic fibers)
- Bone- marrow derived cells: Mast cells, B/T lymphocytes
- Vessels (endo and pericytes)
- Neural tissue
Subcutaneous fat
Langerhans cells
APC (antigen-presenting cells) seen in epidermis)
- Characteristic Birbeck granules seen by electron microscopy
Types of epidermal inflammation
Angiocentric: around blood vessels
- Urticaria, necrotizing vasculitis
Spongiotic: increased fluid between keratinocytes (edema)
- Allergic contact dermatitis
Interface: Inflammation between epidermis and dermis
- Lupus, contact dermatitis
Vesiculo-bullous: blistering between epidermis and dermis (lifting)
- Pemphigus
Panniculitis: inflammation of subcutaneous fat
- Erythema nodosum
Responses to skin injury: proliferation
Hyperplasia= Acanthosis
- Psoriasis
Dysplasia= atypical cell
Neoplasia: benign and malignant
- Benign Epidermal:
- Seborrheic keratosis, Verruca - Pre-malignant Epidermal: Actinic keratosis
- Malignant Epidermal:
- Squamous cell carcinoma, Basal cell carcinoma - Benign Melanocytic: Melanocytic nevus
- “Pre-malignant” Melanocytic:
- Dysplastic/Atypical melanocytic nevus - Malignant Melanocytic: Melanoma
Response to skin injury: storage/deposition
Solar elastosis: dense clumpy deposition of elastic fibers due to chronic sun damage
Secondary amyloidosis: deposition of amyloid in skin
Gout: deposition of birefringent uric acid crystals in dermis surrounded by granulomatous inflammation
Urticaria
Angiocentric skin changes
Often young adults
- Transient, lasts < 24 hrs
- Non-purpuric wheals: Edematous, erythematous papule or plaque
- Intensely pruritic (itchy)
- Angioedema (deep)
- Chronic forms: Urticarial vasculitis, Underlying disease
Pressure
- Dermatographism
Type I hypersensitivity reaction
- Immunologic (IgE-mediated): Mast cell degranulation, Release of histamine, prostaglandins
- Non-immunologic: Mechanical (dermatographism), Temperature
Pathophys:
- Mast cells degranulate: release Histamine, prostaglandins, cytokines
- -> Vascular dilation, Dermal edema, Endothelial activation
- E-selectin/CLA binding
- Angiocentric inflammation: Lymphocytes, neutrophils, eosinophils
- No epidermal changes
Necrotizing vasculitis
Angiocentric skin changes
Seen on Lower extremities
- Palpable purpura= Red macules and papules with dot-like hemorrhage
- Diascopy
Limited to skin or systemic
- Drugs, infection, connective tissue disease, underlying malignancy (Idiopathic in 50%)
Henoch-Schönlein Purpura: seen after strep, viral illness (hematuria, abdominal pain, vasculitis mediated by IgA)
Pathophys:
- Infiltrate of neutrophils with fragmentation (nuclear “dust”)
- Neutrophils chew thru fibrin in vessel walls and lumen (fibrinoid necrosis)
- Hemorrhage due to vessel wall destruction (extravasation–> no blanching)
- Positive DIF (direct immunofluorescence)
Allergic contact dermatitis
Form of Spongiotic dermatosis
Pruritic, well-demarcated, erythematous, edematous papules and plaques with vesicle formation
- Blisters in 1-2 days (Often linear lesions)
- Epicutaneous contact (Poison ivy)
- Scaly with chronicity
Pathophys:
- Type IV reaction= cell-mediated or delayed hypersensitivity
- Antigen taken up by LC; LC to draining LN; present to T helper cells (MHC class II); becomes sensitized
- Sensitization/challenge
Histo:
- Intercellular edema between keratinocytes: May form vesicles
- Langerhans cells in vesicles
- Perivascular infiltrate of lymphocytes, histiocytes, and eosinophils
Psoriasis
Acanthotic process: hyperplasia of epidermis
Erythematous plaques with silvery scale
- Pustules (early)
- Silvery scale (late)
- Often symmetric, B/L: Elbow, knees, scalp, intertriginous, or generalized
- Koebner phenomenon (damage–> lesion)
- Auspitz sign (scale lifted–> bleeding)
- HLA types : Cw6, B13, B17, Bw57
Psoriatic arthritis: seen in 5-8% of psoriasis patients
- higher association with nail bed changes
Histo:
- “Regular” acanthosis
- Parakeratosis
- Neutrophils in scale
- Loss of granular layer
- Thin suprapapillary dermal plate
- Prominent, dilated capillaries
Pathogenesis:
- Lymphocytes
- Autoreactive T cell
- Keratinocytes
- Shortened epidermal cell cycle (28x nl production)
- Vessel alterations: abnormal post-capillary vessels (dilated)
Lupus erythematosis
Interface changes in epidermis/dermis:
Acute Form:
- Facial erythema (malar rash)
- Generalized erythema: Face, arms, neck, dorsal hands
- Bullae
Subacute Form
- Psoriasiform
- Annular vesicular
Chronic Forms
- Discoid lesions (5-10% have systemic disease)
- Scaling, atrophic plaque
- Hypo/hyperpigmentation
- Follicular plugging
- Alopecia
- Panniculitis (50% have systemic disease)
Discoid lupus (confined to skin, may develop systemic disease in 5-10%):
- Localized to skin
- Scaling atrophic plaques
- Pigmentary changes
- Telangiectasia
- Alopecia
- Follicular plugging
Discoid lupus histology:
- Hyperkeratosis (scale)
- Epidermal atrophy= Lymphocytes attacking DEJ (interface)
1. Basal cell vacuolization due to interface
2. Necrotic keratinocytes (attacked by lymphocytes- pyknotic keratinocytes)
3. Pigment incontinence: dump melanin) - Superficial & deep perivascular & perifollicular: Follicular destruction
- Dilated vessels
- Positive ‘Lupus Band’= Granular IgG & C3 along thickened BM
Lichen planus
Interface process
Scaly, flat-topped, violaceous papules and plaques
The 5 Ps:
- Pink to purple
- Pruritic
- Polygonal
- Papules
- Plaques
- Often wrists and ankles; Can occur anywhere including oral mucosa
- Most cases idiopathic
Histo: interface process=
- Superficial band-like lymphocytic infiltrate (DEJ)
- Necrotic keratinocytes
- Hyperkeratosis
- Hypergranulosis (wedge-shaped)
- Irregular acanthosis
- Saw-toothing of rete edges
Pemphigus vulgaris
Vesiculobullous process
- Flaccid blisters; Easily ruptured
- Erosions
- Scalp, mucosa, intertriginous sites
- Nikolsky sign: press lateral edge of blister, it will spread
- Genetic predisposition
- Commonly 40s-50s
- Autoimmune disease
Histo:
- Blistering is Supra-basal (Tombstone pattern where basal keratinocytes still attached to dermis)
- Acantholysis
- Autoantibodies to Desmoglein 3–> destruction of Desmosomes
- vs Bullous pemphigous= entire epidermal layer lifts from dermis (no keratinocytes still resting on basement membrane= sub-basal)
- Sub-epidermal blistering also seen in dermatitis herpetiformis
Erythema nodosum
Panniculitis Tender erythematous nodules on extensor surfaces of lower legs - Dome-shaped, firm erythematous nodules - Self-limited, constitutional symptoms - Seen in young women
Immunologic response to foreign antigens
- Can be due to distal infection (bacterial, viral, TB, fungi), drugs (sulfa, OCPs), sarcoid, IBD, tumors, etc.
Histo:
- Septal
- Mostly chronic inflammation
- Granulomas
- Fibrosis
- Mimicry: Infection, Factitia
Seborrheic keratiosis
Benign Epidermal neoplasia
- Middle age and older
- Oval or round “stuck on” papule or plaque
- Flesh-colored to brown or black
- Rough surface
- Symmetrical, sharp margins
- Sign of Leser-Trélat: multiple developed over short period of time–> underlying malignancy (release of growth factors)
- Cause???- genetics, sun exposure, viral
Histo:
- Basaloid keratinocytes (follicular infundibulum): can grow up or invaginate
- “Horn cysts”= invagination, gives rough appearance
- No melanocytic derivation (keratinocytes!)
Verrucae (warts)
Benign epidermal neoplasia; Also, an infection (HPV)! - Seen at Sites of inoculation - Malignant transformation with immunosuppression - “Black dots” when peeled away Types: - Verruca vulgaris - Verruca palmaris/plantaris - Verruca plana - Condyloma acuminatum
HIsto:
- Benign squamoid proliferation
- Crown-like with vascularized spires; irritation–> bleeding–> black hemorrhagic spots
- Koilocytosis: nucleus with glassy appearance (intranuclear virus)–> crinkled with halo
- Keratohyaline granules within keratinocytes
- HPV genome (typing): immunohistochem, FISH (high or low risk)
- Cell-mediated immune response–> resolution (unless immune suppressed)
Actinic Keratosis
Pre-malignant epidermal changes:
- Rough, scaling, reddish, ill-defined patch or plaque (can see cutaneous horn; may also be wart, carcinoma–> biopsy!)
- Occurs on sun-exposed skin
- UV-radiation induced keratinocyte DNA damage
- Can spontaneously regress (up to 25%)
- May progress to squamous cell carcinoma
Histo:
- Variable atypia; Less than full epidermal thickness
- Hyperkeratosis
- Parakeratosis
- Solar elastosis
- Chronic dermal inflammation
Squamous cell carcinoma
Malignant epidermal neoplasia
- Scaling, erythematous to flesh-colored plaque or nodule
- May be scaly, ulcerated or crusted
- Occurs most often on sun-exposed skin (75% on head and neck)
- Also on mucous membranes and sites of chronic injury (burn scars, irradiated sites, sinus tracts)
2nd most common skin cancer
- UV radiation induced immunosuppression
- Locally invasive
Potential to metastasize
- 2-5% of SCCs related to sun exposure
- Up to 20% of SCCs arising in sites of chronic injury (draining sinuses, burn scars) and mucous membranes
Histo:
- Atypical keratinocytes
- Growth into underlying dermis
- Keratin pearls (altered, denser homogenous keratin formation)
- Hyperkeratosis
- Parakeratosis
Basal cell carinoma
Malignant epidermal neoplasia
- Erythematous patch with central erosion/ulceration and rolled, pearly border OR a pearly papule or nodule
- Telangiectasia
- Seen on sun-exposed skin, most common on face
- Most common skin cancer; most common human malignancy
- Rarely metastasizes but may be locally aggressive
Histo:
- Enlarged basaloid keratinocytes (increased mitoses)
- Individual cell necrosis= malignancy
- Bud and extend into dermis
- Peripheral palisading
- Separation artifact on histologic preparation: due to mucinous stroma- washed away after processing
Melanocytic nevus
Benign melanocytic neoplasia - Most acquired after age 6 months and before age 35 Variable (but uniform) appearance: - Macular or papular - Brown to flesh-colored - Usually <5 mm in diameter
Junctional: present as nest in epidermal-dermal junction
Compound: involves dermis and epidermis
Dermal: neval cells only seen in dermis
Histo:
- Derived from neural crest origin
- Maturation with descent into dermis
Dysplastic nevus
Melanocytic dysplasia
- Controversial entitiy
Abnormal: clinical appearance, architecture, cytology, stroma
Isolated vs dysplastic nevi syndrome
- Clinical phenotype
- Personal and family history
- 100% lifetime risk
Premalignant potential, markers for increased melanoma risk
Histo:
- Irregular nests: bridging (nests coalesce), shoulder (epidermal component descends beyond dermis)
- Cytologic atypia
- Stromal fibrosis, lamellar fibroplasia (collagen, onion-skin layering around rete ridges)
Melanoma prognosis
TNM stage:
- Measured Depth (mm)= thickness (#1 prognostic feature)
- Ulceration (bad sign)
- Mitotic rate (more mitoses, worse prognosis)
- Clark level (obsolete finding- how deep)
- TIL Response (tumor-infiltrating lymphocyte response= good prognosis)
- Regression (bad prognosis: body eradicates part of melanoma)
- Vascular Invasion (mets)
- Microscopic Satellites (bad)
- Gender (F fare better than M)
- Site (extremities except hand and feet do better)
- Stage (metastasized= prognostic indicator)
