Pigmented or erythematous flat lesion on the epidermis

 < 5mm

pigmented or erythematous flat lesion on the epidermis

> 5 mm

Hive

Edematous, transient papule or plaque caused by infiltration of dermis by fluid

• Most common benign tumor in older indivudals
• Occur in >30 years Goljan says > 50 years
• May increase in number with age
• Trunk >> extremities> head and neck
• Common on the face in elderly patients
• Rarely occur suddenlt in large number
• If they do occur in large number it is called Sign of Leser-Trelat. Sign of Leser-Trelat is a paraneoplastic syndrom and is seen most commonly with stmach adenocarcinoma, related to transforming growth factor-α
• Coin-like macules/papules that are raised and can appear verrucoid with a stuck on appearance. Or they can be smooth and greasy appearing. 
• Dermatosis Papulosis is a Seborrheic Keratosis around the face
• Many histological patterns of SK but often times you will see:
• Hyperkeratosis
• Acanthosis
• Basaloid Keratinocytes
• Epidermal invaginations; Keratin-filled horn cysts
• Often contain melanin pigment
• Treatment:
• Cryotherapy
• Curettage
• Shave/Biopsy/Excision

• Reactive hyperplasia in response to growth factors
•  Velvety,thickened skin, hyperpigmented
• Most often found in the axilla, neck, under breasts, groin
• May be a cutaneous marker for benign and malignangt conditions (80% benign)
• AD heritable trait
• Obesity and endocrine abnormalities (diabetes)
• GI malignancies

• Associated with prolonged exposure to the sun (UV radiation)
• Can be thought of as a pre-cancerous condition
• Risk factors also include hydrocarbons and arsenicals (pesticides)
• Course:
• Stable
• Regress
• Progress to SC
• Grossly appear as hyperkeratotic, pearly gray white papules/macules
•  Histologic appearance:
• Hyperkeratosis
• Parakeratosis
• Dysplasia of the lower epidermis (not full thickness dysplasia)
• Solar Elastosis
• Commonly reoccurs when scraped off

• Second most common tumor arising in the sun (BCC 1st)
• 5% rate of metastasizes
• Usually well differentiated
• M>F; 70 yrs of age
• Common on sun exposed areas (head and neck)
• Favor lower lip
• Predisposing Factors:
• UV light
• Industrial carcinogens
• Chronic Ulcers
•  Old burn scars
• Immunosupression
• Xeroderma pigmentosa
• Mutation in P 53-inability to repair UV induced dimers
• Actinic Keratosis
• Flesh colored or erythematous, can be smooth or nodular(warty surface).  Often times if the lesion is nodular then it will be centrally ulcerated.  Firm to the touch.
• Hisologic appearance:
• Hyperkertosis
• Parakeratosis
• Acanthosis
• Dysplasia of entire epidermis
• Extension of tumor into the dermis
• Squamous pearls
• Solar elastosis

• Most common malignant skin tumor
• Locally invasice; rarely metastasize
• Tumor is stromal dependent
• Arises from the basal cell layer of the epidermis
• Multifocal origin so it may be difficult to obtain clear margins.
• Cords of basophillic staining basal cells infiltrate the underlying dermis.
• M>F; 60year (although we are seeing them younger and younger due to tanning beds)
• Seen in areas that get a lot of sun exposure (head and neck)
• Favors the upper lip and higher (general rule)
• Predisposing factors:
• Fair complexion
• UV
• Immunosupression
• Nevoid Basal Cell Carcinoma syndrome
• Gross appearance: Papules/Nodules that have smooth paerly surface and may have a central ulcer.  Telangiectasia.
• Histologically often times a retraction artifact is seen.

Nevoid Basal Cell Carcinoma Syndrome

NBCCS

• AKA Gorlin Syndrome, Basal Cell Nevus syndrome
• Multiple BCC <20 years
• Assocaited with
• Medulloblastomas
• Ovarian fibromas
• Odontogenic keratocyts
• Palmer/plantar pits
• Intracranial calcification
• Rib abnormalities 
• AD
• PTCH gene on 9q22.3
• Receptor for SHH gene product
• Uninhibited activation of smoothened (increased transcription factors)
• PTCH normall keeps smoothened in check

• Benign vs. malignant (Dr. B thinks Malignant)
• Rapidly growing tumor in sun exposed areas (face and dorsa of hands)
• May spontaneously resolve
• Very rarely aggressive
• Varient of SCC
• large crateriform nodule with cental keratin plug 
• Histological appearance:
• Cup shaped
• Keratin plug
• Glassy keratinocytes

• All ages and races but more common in blacks
• Partial to complete loss of pigment producing melaocytes
•  Autoimmune mediated
• Melanocytes are destroyed
• Causes localized to extensive areas of skin depigmentation
• Koebnerization-press on or scratch around the lesion, new lesion develops o spreads.
• May respond to light therapy.
• Histologically can use a brown stain to identify melanocytes and in this condition with this stain no melanocytes are seen
• Often associated with other autoimmune disorders

• Benign localizd hyperplasia of melanocytets 
• In contrast freckles (ephilis) are increased melanin pigmen only
• Linear melanocytic hyperplsic with thinning or elongation of rete pegs
• Lentigo smplex-not caused by the sun
• Actiniv solar lentigo-caused by the sun
• Can progress the a nevi  

• Macules and papules that are tan to black in color, regular in shape and border and are < 5mm diameter
• Histologic appearance:
• Symmetric
• Predominant nest pattern
• Cytologically bland melanocytes
• No dermal mitotic figures
• Maturation-nuclei get smaller with descent into the dermis.
• Neuorization is the maximal point of maturation
• Junctional Nevus- melanocytes are only present in the epidermis
• Compoud Nevus- melanocytes are present in the epidermis and the dermis
• Intradermal Nevus- melanocytes are present in the dermis only.  
• Giant congenital melanoctic nevi have a slightly increased risk for the development of melanoma

• Occur on sun-exposed  and non-sun-exposed areas
• > 5mm diameter
• Variation in pigment with irregular borders
• Clinical Signifcance:
• Isolated lesions: not very significant
• Multiple lesions: probably increased risk of melanoma
• Dysplastic Nevus syndrome: Increased risk for melanoma
• Usually compound or junctional NOT intradermal
• Histological changes:
• Bridging of nests
• Shouldering-in a compound nevus the nests of melanocytes in the epidermis extends farther than the nexts of melanocytes in the dermis
• Dermal fibroplasia (lamellar)
• Single Cell lentiginous proliferation
• Irregular nuclear outlines with hyperchromasia  

• Risk Factors
• UV light-blistering sun burn
• Family History of melanoma
• Dysplastic Moles
• xeroderma pigmentosa
• Incidence is rising-most rapidly increasing cancer worldwide
•  Leading cause of death due to skin cancer
• Clinical Warning Signs
• Itching or pain in a mole
• Develoment of a new pigmented lesion in adult life (60's onward)
• Asymmertic Shape- A
• Irregular borders-   B
• Pigment Variation-  C
• Size > 6 mm          D
• Enlargement of a pre-existing mole - E
• Depth of dermal involvement correlates with prognosis (Breslow level)
• Histological Appearance
• Asymmetric
• Irregualr Nests
• Single Cell Pattern
• Pagetoid Spread-upward movement of melanocyte
• Nuclear Atypia
• Absence of maturation
• Dermal mitotic figures

Spread of melanocytes LATERALLY within the epidermis and papillary dermis, ofter for a polonged period of time

NO metastatic potential  

• Still reported, but ti has less prognostic significance than Breslow level
• Based on the anatomic location of the tumor
• Level I: Confined to epidermis (in situ)
• Never metastasizes
• 100% cure rate
• Level II: Invastion into the papillary dermis
• Thought to not have metastatic potential
• 99% cure rate
• Level III: tumor filling papillay dermis and compressing the reticular dermis
• 95% cure rate
• Level IV: Invasion of reticular dermis (localized)
• 75% cure rate   
• Level V: Invasion of subcutanous tissue
• 39% cure rate

• The most important prognostic indicator
• Perpendicular distance from granular layer to the the deepest atypical melanocyte
• Measured in mm
• Reproducible
• Breslow > 1 mm will get a sentinel node procedure
• Because varying skin thickness is not an issue it is more accurate than Clarks level  

• Most common type (70%)
• Develops on the lower extremities, arms, and upper back 

• Common in the elderly population
• Extension of lentigo maligna (intraepidermal lesion) into the dermis
• Occurs on parts of theface most exposed to the sun
• Least likely to have a verticle phase
• Slow growing-better prognosis  

• No Radial Growth Phase, ONLY VERTICAL GROWTH
• Can be found on any sun-exposed area, most often the trunk
• Poor prognosis  

• NOT related to sun exposure
• Located on the PALM and SOLES or beneath the nail
• Very agressive, poor prognosis
• Occurs more often in Asians and blacks 

• Breslow < 1.7 mm
• Absence/low mitotic index
• Brisk tumor infiltrating lymphocytes (TIL)
• NO regression
• Female Gender
• Location on extremity skin
• Absence of ulceration 

Melanoma Molecular Mechanisms

• Deletions o p16INK4A (CDNK2)
• Unrestricted phosphorylatin of RB
• Unrestricted cell growth
• Deletion of p14ARF
• Inhibitor of cell gowth via interactions with MDM2
• BRAF mutations
• Found in melanomas and nevi
• Part of RAS/RAF/MAP kinase pathway  

• Benign dermal neoplasm of fibroblasts and histiocytes
• Seen in adults-especially young to middle age females
• Firm tan-brown papules less than 1 cm that can flatten with time
• Dimple sign- center of lesion dimples when squeezed
• Some have a history of antecedental trauma suggesting an abnormal response to injury
• ie. Dr. B's exaggerated response to bug bites
• Histologically you see increased fibroblasts that trap collagen (form rings around the collagen) 

Dermatofibrosarcoma Protuberans

DFSP

• Slow growing plaque that later turns nodular
• Usually occurs is mid-adult life
• M>W
• Trunk, proximal extremities is the most common site
• Locally recurrent-intermediate malignancy
• Metastasis < 5%
• Histological Appearance:
• Pin Wheel Appearance
• Fat Trapping 

• Cutaneous T cell lymphoma
• Uncommon but th most common lymphoma to the skin
• Seen in older adults
• Early stage may mimic eczema and it often stays confined to the skin with systemic involvement late in disease with advanced states
• Clinical Progression in disease:
• Patch → plague → nodule
• Sezary Syndrome (Erythrodermic Stage)
• Seeding of blood my malignant lymphocytes
• Circulating cells are called Sezary cells
• Clinical stage is based on body surface area affected
• Histologic Features
•  Psoriasiform epidermal hyperplasia
• Acanthosis
• Hyperkeratosis
• Epidermotropism
• Lymphoctes in epidermis without spongiosis
• Pautrier's microabscesses-collections of neoplastic lymphocytes in spidermis
• Cerebriform nuclei
• Disease of CD4 clonal subset of T cells

• Spectrum of disease is erythema multiforme, stevens-johnson, and Toxic epiderml necrolysis
• Hypersensitivity response
• Herpes simplex virus (HSV)
• Other infections:  mycoplasma, funal mycobacterial
• Drugs: sulfa, penecillin, barbiturates, salicylates, hydantoins, antimalarials
• Malignancies
• Collagen vascular disease: SLE, periateritis nodosa
• idiopathic 50%
• Vesicles and bullae have a targetoid appearance
• Stevens-Johnson
• Extensive disease with oral and ocular involvement
• Involved mucus membranes
• Fever
• More common in children than adults
• Drugs are the most common cause
• Toxic Epidermal Necrolysis
• Extensive sloughing of skin
• Resembles bruns
• Mucosal involvement
• Drugs are more common cause
• Histologic Features
• Superficial perivascular lymphocytic infiltrate usually mild in nature
• Prominent edema of papillary dermis
• Degeneration and necrosis of keratinocyttes leading to full thickness necrosis  

• Annular, polycyclic, blanchable erythema
• Psoriasiform lesions
• Mild Systemic involvement (arthralgias fever, malaise)
• Illness is an intermdiate between SLE and Chronic lupus Erythematosus/ Discoid lupus
• 15% progress to SLE  

• Thin atrophic plaques with hyperpigmentation and hypopigmentation
• Usually no systemic involvement  
• Hair Loss
• Anti-DNA-DNA immunocomlexes deposit in the basement membran and cause degeneration of basal cells and hair shafts (alopecia)
• Positive immunofluorescent band test -complexes deposited along the basement membrane (dermal-epidermal junction. IgM, IgG are both positive.
• Butterfly/Malar rash
• Histological Features
• Hyperkratosis
• Epidermal Atrophy
• Thickened basement membrane
• Interfae changes
• Mucin deposition

• Pruitic
• Purple flat topped/polygonal papules
• Wishham Striae- White scale (white reticular pattern on the surfce)
• Koebner phenomenon-lesions develop in areas of scratching
• Chronic but self-limited disease
• Multiple symmetric lesions on extremitis, especially on the wrists, elbows, glans penis 
• ORAL MUCOSA involvement common
• Associated with Hep C
• Histological Features:
• Dense band like lymphocytic infiltrate that hugs that epidemis
• Hyperkeratosis
• Wedge-shaped hypergraulosis
• "Saw tooth" basal layer
• Individual necrotic keratinocytes (civatte/colloid bodies)

Presents in the 4th-6th decades of life

• M=F
• Autoimmune Blistering
• IgG antibodies target desmoglein 3 in desmosomes
• Desmosomes hold epithelial cells together
• Type II hypersensitivity
• Gross Appearance: 
• Flaccid fragile bullae
• Can break and leave superficial erosions
• Located on the scalp, face, axilla, groin, trunk, and pressure points.
• Oral mucosa involvement
• Nikolsky's Sign- Outer layer of the epidermis separates from the basal later forming a blister with pressure
• Histological Features:
• Intraepidermal, suprabasilar blister
• Basal cells resemble a row or tumbstones
• Mixed dermal inflammatory infiltrate with eosinophils
• Acantholysis
• Eosinophilic spongiosis (eosinophils in epidermis)
• Immunofluorescense- IgG and completement deposits between keratinocytes giving a net like intracellular pattern

• Generally affects the elderly
• Tense Bullae on extremities, intertriginous areas, abdomen, and oral mucosa (to a lesser extend than pemphigus)
• Autoimmine mediated
• IgG antibodies against the hemdesmosome proteins that bind the epidermis to the basement membrane
• Type II hypersensitivity 
• Subepidermal blister without tombstone basal cells and without acantholysis
• Negative Nikolsky Sign
• Blister contains edema fluid and eosinophils
• Immunofluorescence- Linear IgG and complement deposition along the basement membrane. 

• Vesicular not bulous
• Ouccurs in 3-4 decades and M>F
• Puritic burning vesicles, especially on extensor surface of extremities (elbows, knees), upper back, buttocks.
• Vesicles resemble herpes
• Associated with Celiac Disease
• Responds to gluten free diet
• Autoimmune mediated
• IgA antibodies against basement membrane anchoring fibrils
• Subepidermal vesicles containing Neutrophils (neutrophil microabscess)
• Immunofluoresence: Granular IgA deposis in dermal papillae along the basement membrane

• Chronic inflammation of the pilosebaceous units
• Pathogenesis
• Androgens
• Follicular Obstruction
• Propionibacterium acnes
• Heredity
• Drugs, contactants, occulsion
• Histologic features:
• plugged follicle (comedone)
• dilated follicle ( papule, pustule, cyst)
• ruptured follicle ( inflamed nodule)  

• Prototype: Erythema Nodosum
• Inflammation of the subsutaneous fat
• Associations:
• B hemolytic Strep
• Oral Contraceptives
• sulfonamides
• sarcoidosis
• IBD
• Raised tende erythematous nodules on the anterior lower legs
• Histology:Widening of CT septa of the fate with neutrophils, eosinophils, lymphocytes, histiocytes, and multinucleated giant cells
• Eventual septal fibrosis  

• AKA: Tinea, Ringworm
• Infect outer keratin layer of skin
• Erythematousplaque wtih elevated scaly borde
• Histologic features:
• Hyperkeratosis
• Parakeratosis
• Neutrophils in keratin
• Hyphae in keratin-seen in PAS stain

• Warts
• Benign neoplasma caused by HPV
• > 150 subtypes but 16, 18, 33 are associated with SCC
• Occur at any age
• Self limited
• Verruca vulgaris is the common wart 
• Papillomatosis
• Dilated tortuous vessels
• Acanthosis
• Hyperkeratosis
• Koilocytes

• Common especially in children
• Dome-shaped papules with a central keratin filled crater
• Seen on teh face, trunk, and anogenital areas
• Eaisly spread through contact
• DNA poxvirus
• Molluscum bodies are seen-eosinophillic cytoplasmic inclusion in upper layers of epidemis.  Contains viral particles  

• Common superficial ifection
• Most common cause is Staphoccus
• Streptoccus is second most common cause
• Rash usually begins on the face.  Vesicles and pustules rupture to form a honey colored crust. 

1. Megaly (big)
2. Multinucleated
3. Molding
4. Margination
5. Hydrophic changes 

• Well-circumscribed
• Salmon colored papules with silvery scale  
• Usually on extensor surfaces and the scalp
• Pitting of the nail may also be present
• Due to excessive keratinocyte proliferation
• Possible autoimmune etiology:
• Associated with HLA-C
• Lesions often arise in areas of trauma-environmental trigger
• Histology shows:
• Acanthosis
• Parakeratosis
• Collections of neutrophils in the stratum corneum
• Thinning of the epidermis is above the elongated dermal papillae which results in bleeding when scale is picked off (Auspitz sign)
• Treatment invovles corticosteroids, UV light, or immune modulating therapy

• Dermal and subcutaneous infection
• Usually due to S. aureus or S. pyogenes
• Presents as red, tender, swollen rash with fever
• Risk factors include recent surgery, trauma, insect bite
• Can progress to necrotizing fascitis with necrosis of subcutaneous tissue due to infection with anaerobic bacteria
• Surgical emergency  

• Sloughing of skin with erythematous rash and fever
• Leads to sig skin loss
• Due to S. aureus
• Exfolative A and B toxins result in epidermolysis of the stratum granulosum
• Distniquished from toxic epidermal necrolysis by level of skin separation.  Separation in TEN occurs at the dermal-epidermal junction