Dermatopathology and Wound Healing (EXAM 1- MOD)

What are the basic functions of the skin?

• Physical barrier against bacteria, virus, & other organisms

• Regulates body temp

• Prevents dehydration

What are the layers of the skin?

Epidermis, Dermis, Hypodermis/Subcutis

The epidermis protects from….?

Smoke, UV rays, Viruses and Bacteria, and Dryness

The dermis contains…?

blood vessels that produce skin with oxygen and nutrients (most structures located here)

what does the Hypodermis store and control?

stores fat, controls body temp

what are the layers of the epidermis? (superficial to deep)

Stratum Corneum → Stratum lucidum →Stratum granulosum → Stratum Spinosum → Stratum Basale (Come Lets Get Some Beer)

Where does cell division in the epidermis layer occur?

Stratum Basale (Basal layer)

what makes up most of the single layer of cuboidal cells in the Basal layer?

Immature keratinocytes and basal cells

Basal cells are the _______ of the skin

stem cells

What are the major cell types within the basal layer?

Keratinocytes, Melanocytes, and Merkel cells ( Babe Keep Making Meatloaf)

Describe keratinocytes

• Tough, fibrous cells

• 90% of epidermal cells

• Form protective water barrier.

Describe Melanocytes

• Produce melanin

• Protect from UV rays

• Responsible for skin color

Describe Merkel cells

Epidermal sensory cells that help detect light tough sensation

The stratum spinosum (spinous layer) have mostly what type of cells?

Keratinocytes

The “prickle cell layer” is consider the…?

stratum spinosum

what cells are the first line of immunologic defense in the epidermis? and where is located?

Langerhans cells

• located in stratum spinosum

Describe the function of Langerhans cells

• Monitor the environment

• Capture invaders and break them down

• Attach antigens to the cell surface and present them to T cells to trigger immune response

What is the thickness layer of the epidermis?

Stratum Spinosum (Spinous layer)

In the stratum spinosum keratinocytes start producing ?

Keratin

The cells in the spinous layer appear to be what? and why?

• “Spiny”

• Due to desmosome connections and keratin filaments, which provide strength and help resist adhesive forces

There are 3-5 layers of flattened keratinocytes in which layer of the epidermis?

Stratum granulosum (granular layer)

What is formed in the stratum granulosum?

keratohyalin and lamellar granules

keratohyalin and lamellar granules help do what in the granular layer?

• Form waterproof barrier

• Solidify the keratin matrix

• prevent nutrients from getting to more superficial cells

What disintegrates in the upper layers of the granular layer?

Organelles and Nucleus

In the Granular layer cells are….

dying

Which layer of the epidermis does constant shedding and replacement occur?

Stratum corneum (cornified layer)

Which layer of the epidermis is considered the “Major physical barrier?”

stratum corneum

There are 10 to 30 layers of cells as flattened plates or “squames” in this layer of the epidermis. What layer is it?

Stratum corneum (cornified layer)

Dead/ “acellular” outer layer is considered which layer of the epidermis?

Cornified layer

Complete cell turnover in the cornified layer takes how long in young people and elderly people?

• 28-30 days in young people

• As long as 50 days in elderly people

describe the process of proliferation to desquamation through the epidermis.

The Dermal-Epidermal Junction (DEJ) is also known as the….?

Basement Membrane Zone

What does the DEJ contribute to ?

structural integrity and the skin’s barrier function between the epidermis and dermis

How does the DEJ contribute to structural integrity?

• Rete ridges (epidermal ridge)- downward projection of the epidermis

• Dermal papillae - upward projection of the dermis

• This alternating pattern increases surface area which:

  • Forms a strong connection from dermis to epidermis

  • Allows for efficient exchange of nutrients and waste

What are considered flat skin lesions?

Macules and Patches

Describe a Macule

• A flat (NON PALPABLE), hypo/hyperpigmented lesion

• <1cm

what are some examples of a macule?

• Freckle

• lentigo

• post inflammatory hyperpigmentation (PIH)

• some nevi (moles)

Describe a Patch

• Flat (NON PALPABLE), hypo/hyperpigmented area

• >1cm

What are some examples of a patch?

• vitiligo

• cafe au lait spot

• tinea versicolor

• melasma

What are considered raised skin lesions?

Papules, plaques, and nodules

Describe Papules

• Elevated, PALPABLE

• <1cm

what are some examples of papules?

• Some acne

• Warts

• Many viral rashes

• Keratosis pilaris

what are plaques

• Elevated, Palpable

• >1 cm

What are some examples of Plaques?

• Psoriasis

• Dermatitis

• Tinea Corporis

• Some congenital nevi

What are Nodules?

• Solid, rounded lesion

• Diameter is roughly equal to thickness

• Firm lesions that extends deeper into the skin

What are some examples of nodules?

• Epidermal cysts

• Basal cell carcinoma

• Keloid

• Dermatofibroma

• Prurigo nodularis

What are vesicles?

• Fluid filled

• Small blisters (<1cm)

What are some examples of vesicles?

• Chicken pox

• Herpetic lesion

• Poison Ivy

What are Bullae?

• Fluid filled

• Large Blisters (>1cm)

What are some examples of Bullae?

• Poison ivy

• Bullous disorders

What are Pustule?

Vesicle or bulla that contains purulent fluid (pus)

What are examples of pustule?

• Acne pustule

• Folliculitis

• Furuncles

what are considered fluid filled skin lesions?

Vesicles, Bullae, and Pustule

What are the 9 major patterns of skin inflammation?

a. Psoriasiform dermatitis

b. Interface dermatitis

c. Vesiculobullous

d. Vasculitis

e. Spongiotic

f. Panniculitis

g. Nodular

h. Folliculitis

i. Perivascular

What is the representative disease for Psoriasiform Dermatitis?

Psoriasis

Describe the Epidemiology/ Etiology of Psoriasis

• Unknown etiology ( genetic and environment component) affects 1-2% of population

Describe the pathogenesis of Psoriasiform Dermatitis

• The cell cycle moves far too fast; too many new keratinocytes are produced in the basal layer, and they’re pushed to the surface without having proper chance to mature

Describe the histopathology of Psoriasiform Dermatitis

• Rapid epidermal cell turnover→ Marked epidermal thickening of the stratum corneum (Hyperkeratosis- skin producing cells faster than it can shed them)

• Rete ridges are significantly and evenly elongated

• Cornified layer exhibits (Parakeratosis- immaturity of those piled-up cells)

• Accumulation of acute inflammatory cells (neutrophils) within the epidermis

What are the clinical manifestations of Psoriasiform dermatitis?

• Chronic persistent, relapsing, scaling skin condition

• Sharply marginated (clear border) , red plaques with silvery scales

• can see associated arthritis

• EX: lichen simplex chonicus, seborrheic dermatitis

What is the representative disease for Interface dermatitis?

Lichen Planus

What is the epidemiology/etiology of Interface dermatitis?

• Poorly understood, can be related to medications

What is the pathogenesis of interface dermatitis?

• An inflammatory process where infiltrating immune cells directly attack and damage the keratinocytes resting along the DEJ

What is the Histopathology of interface dermatitis?

• Dense infiltrate of lymphocytes (mostly T Lymphocytes) along the DEJ

• Keratinocytes under attack clump tg → form Colloid/Civatte bodies (dense eosinophilic globules)

• Chronic inflammation causes hyperkeratosis and flattening of rete ridges, “Sawtooth” rete ridges in established lesions.

what are the clinical manifestations of interface dermatitis?

• Itchy rash with distinct violaceous papules with angulated borders and flat tops or “Pruritic, polygonal, purple papules”

• Flexor surfaces of extremities, genital area

• Whitish streaks on lesiona are also seen on mucosa (Wickham Striae)

• EX: Lupus, erythema multiforme, fixed drug reaction

What is the representative disease for Vesiculobullous Dermatitis?

Bullous Pemphigoid

What is the Epidemiology/Etiology for Vesiculobullous Dermatitis?

Blistering autoimmune disease that typically occurs in elderly patients

What is the pathogenesis for Vesiculobullous Dermatitis?

Autoantibodies target components of the skin’s basement membrane causing separation of the skin layers and fluid filled space

What is the Histopathology for Vesiculobullous Dermatitis?

• Subepidermal bullae (blisters forms beneath epidermis) or Intraepidermal bullae (blister forms within epidermis)

• Some related VD diseases may have acantholysis (separation of keratinocytes) or hyperkeratosis

• Inflammatory infiltrate within dermis and around blister can vary, commonly including Eosinophils, neutrophils and lymphocytes

what are the clinical manifestations for Vesiculobullous Dermatitis?

• Begins itching (hive like) and then a tense blister develops

• Most commonly on extremities and trunk

• When it breaks, leaves erosion, then hyperpigmentation after blister goes away

• EX: pemphigus, dermatitis herpetiformis, HSV, hand-foot-mouth disease

What is the representative disease for Vasculitis?

Leukocytoclastic Vasculitis (LCV)

What is the epidemiology/etiology of Vasculitis?

• Can occur at any age

• Triggered by infections (especially Staph and Strep), cancers, or medications

What is the pathogenesis of Vasculitis?

• immune complexes (antibodies bound to exogenous antigens) deposit in vessel walls

• Neutrophils destroy vessels and surrounding tissue

What is the Histopathology of Vasculitis?

• Neutrophil infiltration around vessels

• Leukocytoclasia- accumulation of necrotic neutrophil nuclei and debris

• Fibrinoid necrosis - Fibrin protein deposition within and around vessel walls

• RBC extravasation (leakage of blood)

What are the clinical manifestations of vasiculitis?

• inflammatory disorder of small blood vessels

• Palpable purpura

• Lesions may ulcerate or become necrotic

• Arthralgia, myalgia, malaise, involvement of GI tract and other abdominal organs

• EX: IgA Vasculitis, Connective tissue diseases, ANCA-associated vasculitides

What is the Representative disease of Spongiotic Dermatitis?

Allergic Contact Dermatitis

What is the Epidemiology/Etiology of Spongiotic Dermatitis?

• Very Common, thousands of known antigens

• Delayed hypersensitivity reaction

• Immune mediated reaction to a substance that touched the skin

What is the histopathology of Spongiotic Dermatitis?

• Spongiosis (intracellular edema of epidermis)

• Separation of Keratinocytes

• minimal perceptible microscopic changes→ severe blisters w/ fluid filled spaces

• Perivascular inflammation of superficial dermis

• Infiltrate of lymphocytes and eosinophils

What is the pathogenesis of Spongiotic Dermatitis?

Epidermal edema causes separation between keratinocytes

What are the clinical manifestations of Spongiotic Dermatitis?

• Pruritic eruption

• Erythematous papules

• Vesicles and Bullae at contact site

• EX: Drug eruptions, Atopic dermatitis (eczema)

What is the representative disease for Pannicultis?

Erythema Nodosum

What is the Epidemiology /Etiology for Panniculitis?

• More common in females (3:1)

• Associated with infections, IBD, medications

What is the histopathology for Panniculitis?

• Inflammation of the subcutaneous fat

• Septal thickening/fibrosis in some cases of septal inflammation

• Foamy histiocytes and multinucleated giant cells due to necrosis within fat

What are the clinical manifestations of Panniculitis?

• Tender red nodules→ anterior lower legs

• Bruise like patches

• Fever and arthralgias possible

• EX: Erythema Induratum, Nodular vasculitis, Lupus

What is the representative disease for Nodular dermatitis?

Cutaneous sarcoidosis

What is the Epidemiology/Etiology for Nodular dermatitis?

• High incidence in black population in US, Women >Men

• Poorly understood

• Genetic and environmental components

What is the Histopathology for Nodular dermatitis?

• Dense infiltrates of inflammatory cells in dermis

• Macrophages and lymphocytes (sometimes eosinophils and neutrophils) compose nodules

What is the pathogenesis of Nodular dermatitis?

Large, well defined collections of immune cells group tg to form nodules within the dermis

What are the clinical manifestations of Nodular dermatitis?

• Red-brown nodules

• Common on face

• Painful, itchy, or ulcerated lesions\

• “great imitator”, can occur within tattoos and scars

• EX: Prurigo nodularis

What is the representative disease for Folliculitis?

Acne

What is the epidemiology/ etiology of folliculitis?

• Any age possible, very common in adolescents

• Excess sebum production

• Hyperkeratinization (clogging of hair follicles)

• Bacterial colonization (Cutibacterium acnes)

• inflammation

What is the histopathology of folliculitis?

• Inflamed hair follicle

• Follicle becomes plugged with keratin, sebum, and/or debris

• Neutrophilic infiltrate → can form intraepidermal pustules

What is the pathogenesis of folliculitis?

• Follicle becomes plugged

• Follicular wall ruptures

• Contents spill into dermis causing inflammation

What are the Clinical manifestations of folliculitis?

• Follicle based comedones, inflammatory papules, and pustules

What is the representative disease for Perivascular dermatitis?

Urticaria

What is the epidemiology/Etiology for Perivascular dermatitis?

• Affects 15-25% of population, all ages

• Many causes

What is the histopathology for Perivascular dermatitis?

• Mast cell degranulation→ release histamine pro-inflammatory cytokines

• Causes vasodilation and extravasation of fluid in the dermis

• Minimal to no epidermal changes

What is the pathogenesis for Perivascular dermatitis?

Inflammatory reaction clustered around superficial and/or deep dermal blood vessels

What are the clinical manifestations for Perivascular dermatitis?

• Transient papules or plaques, often called hives/wheals

• Possible angioedema/anaphylaxis

• EX: Insect bite reactions, angioedema

Actinic Keratosis (AK), Basal cell carcinoma (BCC), Squamous cell carcinoma (SCC), and Malignant melanoma (MM) are considered __________ lesions.

Neoplastic lesions

Describe Actinic keratosis and It’s histology

• Precancerous lesion

• Caused by sun exposure

• Rough scaly lesion

• Can progress to Squamous cell carcinoma

Histology:

• Dysplastic keratinocytes

• Parakeratosis: retention of nuclei in the stratum corneum

• Thickened stratum corneum