Boards & Beyond:

Dermatology Slides
Color slides for USMLE Step 1 preparation
from the Boards and Beyond Website

Jason Ryan, MD, MPH

2022 Edition

Boards & Beyond provides a virtual medical school curriculm used

by students around the globe to supplement their education and
prepare for board exams such as USMLE Step 1.

This book of slides is intended as a companion to the videos for

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 Table of Contents
Skin............................................................................1 Skin Infections.................................................... 24
Epithelial Cells.......................................................6 Blistering Disorders......................................... 28
Skin Disorders I................................................. 10 Hypersensitivity Disorders........................... 31
Skin Disorders II................................................ 16 Skin Cancer.......................................................... 34
Pigment Disorders............................................ 19 Neurocutaneous Disorders........................... 39
Vascular Tumors................................................ 21

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 Skin
Skin
• Largest organ in the body
• Barrier against infection
• Prevents water loss
• Three layers
• Epidermis: keratinocytes (squamous epithelial cells)

Skin • Dermis: connective tissue, vessels

• Subcutaneous fat (also called hypodermis or subcutis)
Jason Ryan, MD, MPH

Mikael Häggström/Wikipedia Wikipedia/Public Domain

Epidermal Layers Epidermal Layers

• Stratum Basalis • Stratum Lucidum
• Stem cells • Clear layer of dead skin cells
• Stratum Spinosum • Stratum Corneum
• Desmosomes form spines • Anucleated cells
• Stratum Granulosum • Filled with keratin filaments
• Keratohyalin granules
• Form keratin filaments

Mikael Häggström/Wikipedia Mikael Häggström/Wikipedia

1
Dermis Dermatopathology
• Connective tissue • Terms used to describe microscopic findings
• Blood vessels • Used in analysis of skin biopsies
• Hyperkeratosis
• Parakeratosis
• Hypergranulosis
• Spongiosis
• Acantholysis
• Acanthosis

Wikipedia/Public Domain

Hyperkeratosis Hyperkeratosis
• Thickening of stratum corneum
• Excess quantity of keratin Psoriasis Callus

Eisfelder/Wikipedia Public Domain

Nephron/Wikipedia

Parakeratosis Hypergranulosis
• Hyperkeratosis + retained nuclei in stratum corneum • Increased thickness of stratum granulosum
• Indicates hyperproliferation • Classic finding in lichen planus
• Seen in skin diseases (psoriasis) and malignancies

Nephron/Wikipedia Mikael Häggström/Wikipedia

2
Spongiosis Acantholysis
• Fluid accumulation (edema) of epidermis • Loss of connections between keratinocyte
• Seen in eczema, many other skin disorders • Often loss of desmosomes
• “Rounded” keratinocytes
• Detached, floating freely in epidermis
• Key feature of pemphigus vulgaris

KGH/Wikipedia Public Domain

Acanthosis Acanthosis Nigricans

• Diffuse epidermal hyperplasia • Nigricans = darkened
• Elongated rete ridges • Hyperpigmented (dark) plaques on skin
• Spinous layer thickening • Intertriginous sites (folds)
• Classically neck and axillae
Normal Acanthosis
• Hyperkeratosis
• Mild acanthosis
• Associated with insulin resistance
• Rarely associated with malignancy

Rete Ridges

Nephron/Wikipedia Madhero88/Dermnet.com
Public Domain

Skin Lesions Macules and Patches

• Primary lesions • Flat lesions (not raised)
• Directly caused by disease process • Macule: <1cm
• Described using standard terminology
• Patch: >1cm
• Macules, papules, vesicles, bulla
Freckle Stork Bite Birthmark
• Secondary lesions (macule) (Patch)
• Modification of primary lesion
• Or caused by trauma, external factors
• Scale, crust, erosion, fissure, ulcer

Loyna/Wikipedia Abigail Batchelder/Flikr

3
 Papules and Plaques
• Raised lesions
• Papule: <1cm
• Plaque: >1cm
Psoriasis
Mole/nevus
(plaque)
(papule)

Madhero88/Wikipedia
Wikipedia/Public Domain
James Heilman, MD/Wikipedia

Maculopapular Rash
• Collection of small skin lesions
• Some flat (macules)
• Some raised (papules)
• “Morbilliform” – looks like measles
• Common in many disorders
• Drug rash
• Scarlet fever
• Syphilis
• Rubella

Public Domain
Madhero88/Wikipedia

Vesicles and Bulla

• Fluid-filled lesions (blisters)
• Vesicle: <1cm
• Bulla (plural = bullae): >1cm
Chickenpox
(vesicles) Bullous pemphigoid
(bulla)

Madhero88/Wikipedia
Mariegriffiths/Wikipedia
S. Murthy/Slideshare

4
Pustule Wheal
• Pus-filled vesicle • Smooth, elevated papule or plaque
• White center • Surrounded by erythema (redness)
• Itchy
• Caused by dermal edema
Pustular psoriasis Acne • Component of urticaria (allergic reaction)

Wikipedia/Public Domain
Public Domain
Public Domain

Scale Crust
• Secondary lesion • Secondary lesion
• Peeling/flaking of stratum corneum • Dried exudate of skin lesion

Impetigo
Psoriasis

Eisfelder/Wikipedia
CNX OpenStax/Wikipedia
Mikael Häggström/Wikipedia

Narrow tear with walls

Epidermis or dermis

Epidermis

Epidermis/Dermis

Madhero88/Wikipedia

5
 Epithelial Cells
Epithelial Cells
• Form the epithelium
• Line cavities/surfaces of body
• Skin, lung, GI tract
• Secrete substances (endocrine/exocrine glands)
• One of four types of animal tissue:
Epithelial Cells • Muscle
• Nerve
Jason Ryan, MD, MPH • Connective

Basement Membrane Basement Membrane

• Fibrous, extracellular matrix of proteins • Two layers
• Anchors epithelial cells to connective tissue • Basal lamina
• Extracellular matrix secreted by epithelial cells
• Contains laminin proteins
• Type IV collagen (Goodpasture’s/Alport syndrome)
• Reticular lamina (reticular connective tissue)
• Reticular = like a net
• Anchors basal lamina to connective tissue

Basement Basal Lamina

Membrane
Connective Tissue
Wikipedia/Public Domain

Cell Polarity Cell Polarity

• Sheets of epithelial cells bind together • Side facing cavity/lumen: apical membrane
• Different functions for each side of cell (“polarized”) • Lumen of blood vessel
• Lumen of GI tract
• Lumen of nephron
• Outside of body
• Side away from cavity/lumen: basolateral membrane

Basement Basement
Membrane Membrane

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Tubular Epithelial Cells Epithelial Cell Junctions
Lumen (Urine) Interstitium/Blood • Join plasma membranes of adjacent cells
Na+
• Four types:
• Tight junctions
Na+ ATP
• Adherens junctions
K+ K+
• Gap junctions
2Cl-
• Desmosomes

K
K
Cl-

Mg2+ Ca2+
Wikipedia/Public Domain

Tight Junctions Adherens Junctions

Occluding Junctions or Zonula Occludens Belt Desmosomes or Zonula Adherens

• Seals two cell membranes together • Found below tight junctions

• Barrier to paracellular movement between cells • Anchors cells to one another
• Found near apical membrane • Forms belt around cells
• Most apical adhesion between cells • Cadherin
• Built from key proteins: • Cell membrane glycoprotein
• Occludin • Attach to actin filaments in cells
• Claudin

TJ Wikipedia/Public Domain TJ
AJ
Basement Basement
Membrane Membrane Wikipedia/Public Domain

Cadherin Desmosomes
Spot Desmosome or Macula Adherens

• Calcium-dependent adhesion (CAD) proteins • Macula = Latin for spot

• Glycoproteins • “Spots” of cell-cell attachment (not belts)
• Many subtypes • Common in the skin
• E-cadherin: lost in some forms of breast cancer • Attached to intermediate filaments
• Made of keratin
• Found in cell cytoplasm
• Linked by cadherins

Wikipedia/Public Domain

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Keratins Hemidesmosomes
• Tough, fibrous structural proteins • Similar to desmosomes
• Found in hair, skin • Contain intermediate filaments of keratin
• Also horns, claws, hooves • Linked by integrins
• Keratin monomers assemble intermediate filaments • Attach epithelial cells to basement membrane
Microfilaments • Laminin (basal lamina), collagen
7-9nm

Intermediate
10nm

Microtubules

25nm Wikipedia/Public Domain

Gap Junctions Epithelial Junctions

• Channel connections Apical
• Connexins: protein molecules Claudins/Occludins TJ Side
• Form structure called connexon
Cadherin AJ
• Allow small molecules to pass
• Too small for proteins, nucleic acids Cadherin/ DM
Keratin IF

Gap Connexins
Integrin/
Keratin IF
Basolateral
HemiDM

Wikipedia/Public Domain Basement Membrane

Epithelial Cell Types Epithelial Cell Types

OpenStax College/Wikipedia

8
Skin Disorders
• Pemphigus vulgaris
• Autoantibodies to desmosomes
• Bullous pemphigoid
• Autoantibodies to hemidesmosomes

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 Skin Disorders I
Acne
• Inflammation of hair follicles and sebaceous glands
• Exocrine glands in skin in dermis
• Secrete oily substance called sebum

Skin • Often contain hair follicles (“Pilosebaceous unit”)

• Complex, multifactorial etiology

Disorders I
Jason Ryan, MD, MPH

Wikipedia/Public domain

Acne Acne
• Sebaceous glands enlarge at puberty • Sebum: growth medium for bacteria
• ↑ androgens → ↑ sebum • Propionibacterium acnes
• Adolescent acne: men > women • Cutibacterium acnes
• Men with androgen insensitivity: no acne
• Anaerobic bacterium
• Women with excess androgens (PCOS): acne
• Normal skin flora
• Increased sebum and keratin
• Keratinocytes line hair shafts → keratin
• Blocks ducts
• Bacterial growth behind blockage

Wikipedia/Public Domain

Acne Acne
• Comedones allow bacterial growth • Affects most hormone-responsive glands
• Comedo: debris blocking sebaceous duct (bumps on face) • Face, neck, chest, upper back
• Comedone: plural of comedo
• Microcomedo: microscopic comedo (not visible)
• Lipid-rich environment for bacterial growth
• Bacteria use triglycerides in sebum as fuel
• Inflammation from bacterial proliferation

Wikipedia/Public Domain

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Acne Acne
Treatment

• Multiple lesion types • Benzoyl peroxide (topical)

• Open comedos: blackheads • Breakdown keratin, unblocks pores (comedolytic)
• Closed comedos (by skin): whiteheads • Bactericidal to P. acnes
• Inflammatory lesions (papules/pustules) • Antibiotics
• Scarring and hyperpigmentation may occur • Decrease P. acnes colonization of skin
• Clindamycin and erythromycin
• Retinoids (vitamin A derivatives)

Benzoyl Peroxide
BruceBlaus/Wikipedia

Isotretinoin Seborrheic dermatitis

Accutane

• 13-cis-retinoic acid • Red plaques with scale (flaky skin)

• Metabolites bind to nuclear receptors • Occurs on face and scalp
• Retinoic acid receptors (RAR) • Areas with lots of sebaceous glands
• Retinoid X receptors (RXR) • Poorly understood pathogenesis
• Decreases keratin production in follicles • No inflammation of sebaceous glands
• Less follicular occlusion • Associated with fungal infection by Malassezia
• Highly teratogenic • Treatment: topical antifungals and corticosteroids
• OCP and/or pregnancy test prior to Rx

Seborrheic dermatitis Melanocytic Nevus

Moles

• Benign neoplasm of melanocytes

• Tan/brown pigmented lesions
• Uniform color
• Often round or oval shape
• Usually <6mm

Roymishali/Wikipedia
Wikipedia/Public Domain

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Melanocytic Nevus Melanocytic Nevus
Moles Moles

• Congenital • Rarely develop dysplasia → melanoma

• Present at birth • Atypical features may warrant biopsy/removal
• Often have hairs growing from lesion • Not removed prophylactically for prevention
• Acquired
• Appear in childhood
• Increase in number during adolescence
• Peak count in 30s
• Regress with age

Wikipedia/Public Domain

Acquired Nevi Pseudofolliculitis barbae

Razor bumps, shave bumps

• Junctional nevi • Inflammation from trapped hairs

• Growth along dermal-epidermal junction • Associated with shaving
• Often found in children
• Entrapment of recently cut, very short hairs
• Compound nevi • Firm papules/pustules in area of beard growth
• Growth extends into dermis
• Common in black men (up to 80%)
• Intradermal nevi
• 3% white men
• Loss of junctional lesion
• Found only in dermis
• Common in adults

Mikael Häggström/Wikipedia Wikipedia/Public Domain

Psoriasis Psoriasis
• Chronic inflammatory skin disorder
• Well-demarcated plaques
• Pink or salmon colored
• Silver-white scale
• Most commonly on extensor surfaces
• Knees
• Elbows

Jacopo188/Wikipedia

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Psoriasis Psoriasis
• Pathogenesis poorly understood • Acanthosis (thickening of epidermis)
• Combination of genetic and environmental factors • Parakeratotic scaling
• Believed to be autoimmune • Retained nuclei in stratum corneum
• Indicates hyperproliferation
• Strong association with HLA-C
• Stratum spinosum
• Increased in size
• Stratum granulosum
• Thinned or absent
• Munro microabscesses
• Neutrophils in stratum corneum

Mikael Häggström/Wikipedia

Psoriasis Dermis blood vessels close to surface Psoriasis

Scale breaks → bleeding (Auspitz sign)

• Most common type: plaque psoriasis

• Multiple other less common subtypes
• Guttate psoriasis
• Pustular psoriasis
• Erythrodermic psoriasis
• Inverse psoriasis

Public Domain

Psoriasis Rosacea
• Commonly involves nails • Common skin disorder (3% population)
• Nail pitting • Affects adults > 30
• Onycholysis (separation of nail from nailbed)
• Celtics and Northern Europeans: greatest risk
• About 1/3 of patients develop psoriatic arthritis • Affects light-skinned individuals
• Seronegative spondyloarthritis
• More common in patients with nail findings

Public Domain

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Rosacea Rosacea
Other features

• Inflammatory skin condition • Facial flushing

• Complex, poorly understood pathology • Often triggered by environmental stimuli
• Cold, heat, sun, hot drinks, spicy foods, alcohol
• Chronic redness of nose and cheeks
• Papules and pustules • Phymatous rosacea
• Skin hypertrophy
• May look similar to acne but no comedones
• Thickened skin
• Most commonly on nose (rhinophyma)

M. Sand et al./Wikipedia RicHard-59/Wikipedia Public Domain

Seborrheic keratosis Seborrheic keratosis

• Common benign tumors • Flat
• Proliferation of immature keratinocytes • Well-demarcated
• Occurs in older patients (>50) • Round or oval
• Arise spontaneously • Dark, velvety surface
• Commonly on trunk • “Stuck on”

James Heilman, MD

Seborrheic keratosis Leser-Trelat Sign

• Dark cells similar to basal skin cells • “Explosive onset” of multiple itchy SK lesions
• Keratin-filled cysts (“horn cysts”) • Probably caused by cytokines
• Associated with malignancies
• Gastric adenocarcinoma most common

James Heilman, MD

KGH/Wikipedia

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Verrucae Verruca Vulgaris
Cutaneous Warts

• Warts • Most common manifestation of HPV infection

• Cellular proliferation caused by HPV • Transmitted by contact with virus
• Many types • Common on hands
• Verruca vulgaris (skin - most common) • Epidermal hyperplasia
• Verruca plana (skin - flat wart)
• Koilocytosis
• Condyloma acuminatum (venereal warts)
• Cytoplasmic clearing (“halos”) around nucleus

Public Domain Wikipedia/Public Domain

15
 Skin Disorders II
Erythema Nodosum
• Type IV hypersensitivity reaction
• Panniculitis

Skin
• Inflammation of subcutaneous fat
• Often idiopathic
• Many triggers:

Disorders II •
•
Infection (most commonly Strep)
Crohn’s disease (may precede flare)
• Sarcoidosis
Jason Ryan, MD, MPH
• Coccidioidomycosis

Erythema Nodosum Erythema Nodosum

Pathology Findings

• Painful, red nodules • “Septal panniculitis”

• Most commonly on shins • Inflammation of septa of fat between dermis and fascia
• Contrast with “lobular”: inflammation of fat lobules

Specialclass/Sideshare
James Heilman, MD

Lichen Planus Lichen Planus

• Rare, chronic inflammatory skin disorder • 6Ps
• “Lichen” = tree moss • “Pruritic, Purple, Polygonal, Planar, Papules and Plaques”
• “Planus” = flat Lichen on tree • Itchy (often intense)
• Occurs in adults • Purple flat lesions
• Unknown pathogenesis • Multiple, symmetric usually on arms/legs/wrists
• Resolves spontaneously over years • Wrists, ankles are common sites
• Associated with hepatitis C

James Heilman, MD

16
Lichen Planus Lichen Planus
• Mucosal involvement • Lymphocytes at dermal-epidermal junction
• Mouth, tongue • Hyperkeratosis
• Glans penis
• Hypergranulosis
• Wickham striae: white dots/lines • “Sawtooth” pattern of rete ridges
• Caused by hypergranulosis (classic feature of LP)
• Best seen on oral lesions

G Salunkhe/Slideshare

James, Candice, Mai/Wikipedia

Pityriasis Rosea Pityriasis Rosea

• Acute, self-limited skin rash • Begins with “herald patch”
• Eruption of skin lesions • Single red/salmon-colored lesion
• Round or oval
• Self-limited
• Well demarcated
• Resolves 2-3 months
• Chest, neck, or back
• Usually no treatment required • Days later: Multiple lesions on trunk James Heilman,MD /Wikipedia

• Cause unknown (possibly viral) • Multiple similar, smaller lesions

• Groups of lesions
• Follow skin lines on back
• “Christmas tree distribution”

Pityriasis Rosea Burns

Depth Classification

Depth Degree Skin layers

Superficial 1st Epidermis
Superficial partial thickness 2nd Epidermis, some dermis
Deep partial thickness 2nd Epidermis, most dermis
Full thickness 3rd Epidermis and dermis
4th degree 4th Underlying tissue

James Heilman,MD /Wikipedia

17
Superficial Burn Superficial Partial Thickness
1st Degree Burn

• Epidermis only • 2nd degree

• Painful, red, blanch with pressure • Epidermis and some dermis
• Looks like sunburn • Often form blisters
• No blisters • Painful, red
• Heal within 7 days • Blanch with pressure
• Minimal treatment required • Heal within 7 to 21 days

Bejinhan/Wikipedia
Snickerdo/Wikipedia

Deep Partial Thickness Full Thickness 3rd Degree Burn

• 2nd degree • 3rd or 4th degree

• Epidermis, most dermis • Entire epidermis and dermis
• Erythematous, yellow or white • Can involve underlying tissue (4th degree)
• Almost always blister • Fat, fascia or muscle
• Easily unroofed (tissue moves) • Painless
• Painful to pressure only • Scarring with wound contracture
• Do not blanch
4th Degree Burn
• Usually > 21 days to heal
• Heal with scarring
Wikipedia/Public Domain

Wikipedia/Public Domain

Sunburn Sunburn
• Delayed inflammatory response of skin • Damage to epidermis and dermis
• Caused by ultraviolet radiation (UVR) • UV radiation → DNA damage → apoptosis
• Two forms UV radiation • “Sunburn cells”: keratinocytes undergoing apoptosis
• UVB radiation: wavelength 280 to 320 nm • Vasodilation
• UVA radiation: wavelength 320 to 400 nm
• Release inflammatory mediators
• Both may cause sunburn • Self-limited
• UVB range most effective at causing sunburn

Wikipedia/Public Domain

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 Pigment Disorders
Melanin
• Black/brown pigment
• Gives color to skin and hair Tyrosine

Pigment
• Protects from ultraviolet radiation
• Formed from amino acid tyrosine

Disorders
Jason Ryan, MD, MPH

Public Domain

Melanin Freckles
• Synthesized in melanocytes • Small brown/dark macules (flat)
• Specialized secretory cells • Can darken on exposure to sun
• Derived from neural crest
• Increased amounts of melanin
• Found in basal layer of epidermis • Normal melanocyte number/density
• Synthesize melanin in melanosomes Mikael Häggström/Wikipedia

• Melanosomes transferred to keratinocytes

Loyna/Wikipedia

Albinism Albinism
Oculocutaneous Albinism (OCA) Oculocutaneous Albinism (OCA)

• Family of genetic disorders • Hypopigmentation of hair, skin, eyes

• Autosomal recessive • White hair, pink skin color, blue eyes
• Absent/reduced melanin synthesis in melanocytes • ↑ risk of sunburns
• Normal number of melanocytes • ↑ risk of skin cancer
• Most common forms: ↓ activity tyrosinase • No UV light protection
Melanin
• Basal cell carcinoma
• Squamous cell carcinoma
Tyrosinase
• Melanoma

Tyrosine DOPA quinone

Muntuwandi/Wikipedia

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Melasma Melasma
• Acquired hyperpigmentation • Triggered by UV light in susceptible woman
• Irregular areas of tan/dark macules on face • ↑ melanin synthesis
• Often symmetrical • Onset often with pregnancy or OCP
• Sun-exposed areas of face • ↑ estrogen
• “Mask of pregnancy”
• Most common in women with dark complexions
• May resolve after pregnancy
• Cosmetic problem
• Treatment:
• Sun protection
• Skin lighteners: Hydroquinone (inhibits tyrosinase)

Kylie Aquino/Flikr

Vitiligo Vitiligo
• Acquired, localized pigment disorder • Dark skinned individuals
• Autoimmune destruction of melanocytes • Obvious areas of depigmentation
• Asymptomatic depigmented (white) macules/patches • Light skinned individuals
• Failure to tan in localized region
• No clinical signs of inflammation (warmth)
• Treatment: steroids, immunosuppressants

James Heilman, MD/Wikipedia James Heilman, MD/Wikipedia

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 Vascular Tumors
Blood Blister
• Traumatic bleeding in dermis
• Intact epidermis

Vascular
• Many vascular tumors look similar
• Diagnosis by patient characteristics
• Single vs. multiple

Lesions
Jason Ryan, MD, MPH

Esinam/Wikipedia

Angiosarcoma Angiosarcoma
• Rare tumor of blood or lymph vessels • Occur in liver
• Sarcoma = tumor of mesenchyme origin • Associated with vinyl chloride exposure
• Angio = blood vessel (endothelial origin) • Occur in breast
• Lymphangiosarcoma = derived from lymph endothelium • Often following radiation therapy
• Hemangiosarcoma = derived from vascular endothelium • Often in setting of lymphedema after mastectomy
• Hemangioma = benign version
• Purple nodules or plaques
• Poor prognosis

Hai Trieu/Slideshare

Angiosarcoma Bacillary Angiomatosis

• Occur beneath skin • Zoonotic infection by Bartonella
• Usually head and neck (sun exposed areas) • Bartonella quintana and Bartonella henselae
• Often scalp or face • End-stage HIV and AIDS patients
• Arise from dermis
• Systemic infection → blood vessels in skin
• Older, white males
• Presents as numerous red/purple nodules
• Median age: 65 to 70
• Male to female ratio: 2:1 • Similar appearance to Kaposi sarcoma

Wikipedia/Public Domain

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Kaposi Sarcoma Pyogenic Granuloma
Lobular capillary hemangioma

• Common in HIV/AIDS • Benign vascular tumor

• Angioproliferation • Blood vessel hyperplasia due to growth stimuli
• HHV-8 (Human Herpesvirus-8) • Most often on skin
• Key differences from bacillary angiomatosis • Trunk, arms, legs, head, neck
• Kaposi Sarcoma: Lymphocytes • Can be mucosal: lips, gums
• BA: Neutrophils/lymphocytes • Classic stimuli: pregnancy and trauma
• Often bleed profusely
• Surgically removed

Wikipedia/Public Domain
Makotosan/Wikipedia

Cherry Hemangioma Cystic Hygroma

• Benign capillary proliferations • Congenital malformation (newborns)
• Common in middle-aged or elderly • Large cyst containing lymph (benign)
• Develop with aging • Caused by obstruction of lymph drainage
• Usually multiple • Classically develops on neck
• Classically on the trunk
• May bleed from trauma

Timothyjosephwood/Wikipedia
Public Domain

Cystic Hygroma Glomus Tumor

• Often identified on prenatal ultrasound • Glomus body
• Increased risk of fetal aneuploidy and malformations • Structure in dermis of skin
• Trisomy 21 (Down) and Turner syndrome (XO) • Most numerous in fingers and toes
• Cardiac and skeletal malformations • Contains modified smooth muscle cells
• Regulates skin temperature
• Increased risk of miscarriage or fetal death
• Shunts blood away from surface in cold
• Often found together with nuchal translucency
• Preserves heat

Wikipedia/Public Domain

Nevit Dilmen/Wikipedia

22
Glomus Tumor Strawberry Hemangioma
• Benign growth of modified smooth muscle cells • Benign hemangioma
• Occurs in fingers and toes • Excess proliferation of blood vessels
• Usually at tips/ends • Appear in newborns
• “Subungual” = under nailbed • Common: Up to 10% Caucasian babies in some studies
• Usually a single lesion
• Pink/purple papule or nodule
• Usually not present at birth
• Painful especially when exposed to cold
• Usually identified first few days/months after birth
• “Paroxysms of pain”
• Involute within few years
• “Cold sensitivity”

Zeimusu /Wikipedia

Strawberry Hemangioma Nevus Simplex

Stork bite/Salmon Patch

• Capillary malformation (not a tumor)

• Common on eyelids or back (nape) of neck
• “Birthmark”
• Pink-red macule
• Up to 60 percent of infants
• Fade first few years of life

Zeimusu /Wikipedia

Wierzman/Wikipedia

Nevus Flammeus
Port Wine Stain

• Malformation of dermal capillaries and venules

• Slow/low blood flow
• Pink/red patches
• Often unilateral
• Blanch when pressed
• Do not regress
• Grow as child grows
• Sturge-Weber syndrome
Lee Health/Vimeo

23
 Skin Infections
Impetigo
• Superficial skin infection
• Neutrophils collect beneath stratum corneum

Skin
• Macules → papules → rupture → erosions
• Dried sebum → “Honey-colored” crust
• Highly contagious
Infections
Jason Ryan, MD, MPH

CNX OpenStax/Wikipedia

Impetigo Impetigo
• Impetigo contagiosa (non-bullous) • Bullous impetigo
• Traditional, most common form • Seen in children
• Face and extremities • Trunk commonly involved
• Caused by S. aureus • S. aureus
• Also “Beta-hemolytic step” – mostly S. Pyogenes (group A)
• Honey crusted lesions

Public Domain

CNX OpenStax/Wikipedia

S. Aureus Exfoliative Toxin Scalded Skin Syndrome

Exfolatin

• Destroys keratinocyte attachments • Newborn disease

• Cleaves desmoglein 1 complex • Colonization of skin with S. Aureus
• Desmosome protein • Diffuse exfoliative toxin
• Links keratinocytes together
• Classically occurs 3 to 7 days of age
• Affects stratum granulosum • Fever, diffuse erythema
• Leads to bullous impetigo • Sloughing of skin
• Damage intraepidermal Public Domain

• Heals completely with no scar

• Nikolsky’s sign: skin slips off with gentle tug
• Treatment: antibiotics
Public Domain Mikael Häggström/Wikipedia

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Erysipelas and Cellulitis Erysipelas
• Bacterial skin infections that often overlap • Superficial dermis
• Differ mainly by layer of skin involvement • Young children and older adults
• Skin break/trauma → bacterial entry • Usually Group A strep (S. Pyogenes)
• Redness, warmth • Acute onset: fevers, chills, rash
• Sometimes fever • Clear demarcation rash/normal skin
• Usually unilateral
• Most common on legs (lower extremities)
• Erysipelas also on face

Wikipedia/Public Domain

Erysipelas Cellulitis
• Deep dermis
• Subcutaneous fat
• Middle-aged and elderly (rarely children)
• Group A strep (S. Pyogenes) or S. Aureus
• Slower onset
• Rash, focal pain, warmth over days
• Ill-defined, spreading border

Wikipedia/Public Domain
Wikipedia/Public Domain

Cellulitis Skin Abscess

• Collection of pus (neutrophils, bacteria)
• Walled-off in dermis or subcutaneous space
• Usually S. aureus
• Red, painful nodule
• Tense, raised skin
• May complicate cellulitis/erysipelas
• Usually requires incision and drainage

Pshawnoah/Wikipedia

25
Skin Abscess Necrotizing Fasciitis
• Infection of fascia
• Involves muscle fascia and subcutaneous fat
• Destruction (necrosis) of tissue above fascia

BruceBlaus/Wikipedia

Pousettet/Wikipedia

Necrotizing Fasciitis Necrotizing Fasciitis

• Skin color changes: red-purple-blue-gray-black • Crepitus
• Bullae • Crackling sound when skin is pressed
• From gas under skin
• Pain and tenderness
• Methane and CO2 from bacteria
• May be “out of proportion to exam”
• Apparently minor rash with exquisite tenderness
• Patient may mistake infection for muscle injury
• Eventually pain stops (anesthesia) from nerve destruction

Public Domain

Necrotizing Fasciitis Necrotizing Fasciitis

• Often fulminant and deadly
• Infection spreads along muscle fascia
• Poor blood supply → uncontrolled spread
• Requires urgent surgical debridement

Piotr Smuszkiewicz/Wikipedia

Public Domain

26
Necrotizing Fasciitis Necrotizing Fasciitis
• Type 1: • Classic case:
• Polymicrobial • Minor skin trauma
• Often anaerobes (Bacteroides, Clostridium, etc.) • Or diabetic/immunocompromised after surgery
• Strep, staph, others • Redness/warmth (can be confused with cellulitis)
• Occurs in diabetics, immunocompromised, vascular disease • Pain out of proportion to exam
• Usually occurs following surgery • Fever, hypotension
• Type 2:
• Group A strep (sometimes Staph)
• Occurs in otherwise healthy people after skin injury

27
 Blistering Disorders
Blisters
• Fluid-filled skin lesions
• Separation of skin layers Frazzmatazz/Wikipedia
• Space filled with fluid

Blistering •
•
May rupture
Vesicle: <1cm

Disorders •
•
Bulla (plural = bullae): >1cm
Many causes
Jason Ryan, MD, MPH • Burns
• Friction

Pemphigus Acantholysis
• Pemphig: from Greek word for blister • Loss of connections between keratinocytes
• Hallmark: acantholysis • Often loss of desmosomes
• Loss of connections between keratinocytes • “Rounded” keratinocytes
• Involve mucous membranes (mouth) and skin • Detached, floating freely in epidermis
• Subtypes: • Key feature of pemphigus vulgaris
• Pemphigus vulgaris (most common)
• Pemphigus foliaceus
• IgA pemphigus
• Paraneoplastic pemphigus

Public Domain

Pemphigus vulgaris Pemphigus vulgaris

• Autoantibodies against desmoglein • Large, flaccid bullae that easily burst (not tense)
• Component of desmosomes • Often few intact bullae, most rupture and scabbed
• Type II hypersensitivity reaction
• Often presents first with oral bullae and ulcerations
• Disrupts connections in stratum spinosum • Painful chewing/swelling
• Fluid collects above basal layer
• Occurs mostly in adults (30 to 60)
• Nikolsky’s sign
• Skin slips off with gentle tug
• Also seen in Staph Scalded Skin (child)
• Also seen in Stevens-Johnson syndrome

Mikael Häggström/Wikipedia Public Domain Public Domain

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Pemphigus vulgaris Bullous pemphigoid
• Classic finding: (+) immunofluorescence for IgG • “Pemphigoid”: looks like pemphigus
• “Reticular” pattern: like a net • Autoantibodies against hemidesmosomes
• Treatment: immunosuppressants • Bullous pemphigoid antigens (proteins)
• Increased mortality: infection, side effects of Rx • BP180, BP230
• Attach epithelial cells to the basement membrane

Emmanuelm/Wikipedia

Bullous pemphigoid Bullous pemphigoid

• Bullae are subepidermal, nonacantholytic
Eosinophils in blister
• Less fragile (flaccid) than pemphigus vulgaris
• Numerous intact, tense bullae
• Less ruptured bullae with scabs
• Biopsy: Eosinophils and lymphocytes
• Immunofluorescence: line at base of epidermis

Public Domain
Slideshare/Public Domain

Public Domain

Bullous pemphigoid Dermatitis Herpetiformis

• Occurs in the elderly (median age 80 in one study) • Skin condition associated with celiac disease
• Rarely involves mouth • Herpes-like lesions on skin
• Absent Nikolsky's sign • Papules/vesicles in bilateral groups ("herpetiform")
• Treatment: immunosuppressants • Pruritic (itchy)
• Also increased mortality • Classically on extensors: elbows, knees
• Less than pemphigus
• Less bullae rupture → less chance of infection

Madhero88/Dermet.com

29
Dermatitis Herpetiformis Dermatitis Herpetiformis
• IgA deposition in dermal papillae IgA Deposition at tips of
dermal papillae on IF
• Numerous, small lesions at tips of dermal papillae
• Occurs in individuals with genetic gluten sensitivity
• Antibodies triggered by gluten cross-react at skin
• Biopsy: microabscesses (spaces) at tips of papillae
• Neutrophils

Slideshare/Public Domain

Slideshare/Public Domain

Antibody Blistering Disorders

Antibodies Target Location

Stratum
Pemphigus IgG Desmosomes
Spinosum
Bullous Basement
IgG Hemidesmosomes
Pemphigoid Membrane
Dermatitis --
IgA Dermal papillae
Herpetiformis (Gluten-related)

30
 Hypersensitivity Disorders
Allergic Skin Reactions
• Urticaria = hives
• Urticaria = pruritic, raised wheals and angioedema

Hypersensitivity
• Angioedema = deep mucocutaneous swelling

Disorders
Jason Ryan, MD, MPH

Urticaria Urticaria
• Allergic skin reaction • Usually acute and self-limited
• Usually caused by mast cell degranulation • Resolves within days/weeks
• Type I hypersensitivity reaction • May be treated with antihistamines and steroids
• Antigen binding to IgE antibodies on mast cells
• May be a component of anaphylaxis
• Histamine release
• Wheezing
• No changes to epidermis • Mucosal swelling (lips/tongue)
• Dermal edema • Hypotension
• Dilation of lymph vessels • Syncope
• For fluid drainage

James Heilman, MD/Wikipedia

Atopic Dermatitis Atopic Dermatitis

Eczema Eczema

• Chronic disorder with flares/remission • Over 80% patients: ↑ serum IgE levels
• Also a hypersensitivity disorder • 70% of patients: family history of atopic diseases
• Complex, incompletely understood pathogenesis • Commonly co-occurs with allergic rhinitis/asthma
• T-cells, cytokines • “Atopic march”
• Usually “extrinsic”: reaction to environmental antigens • Filaggrin
• Less common form: intrinsic • Protein of stratum corneum
• Usually occurs in children • Filaggrin deficiency impairs skin barrier
• Filaggrin gene mutations → increased risk of eczema
• Red, pruritic (itchy) rash
• Skin dry and scaly
• Easy entry of allergens

Eisfelder/Wikipedia

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Atopic Dermatitis Contact Dermatitis
Eczema

• Babies: face (cheeks) and scalp • Similar clinical features to eczema

• Children/adults: • Localized to area of skin contact with allergen
• Thickened (“lichenified”) plaques • Type IV hypersensitivity disorder
• Skin flexures
• Antecubital and popliteal fossae

Care_SMS/Flikr

Gzzz/Wikipedia Wikipedia/Public Domain

Dr.khatmando/Wikipedia

Contact Dermatitis Drug Rash

• Classic causes (irritants) • “Non-immediate” reaction to drug
• Poison ivy • Often seen with some penicillin antibiotics
• Nickel (jewelry)
• Maculopapular
• Laundry detergents
• Itchy or may be non-pruritic
• Treatment:
• Absence of fever, wheezing, joint pain
• Remove irritant
• Steroids • Days or weeks after starting drug
• Type-IV (T-cell-mediated) mechanism

Romano A et al. Diagnosis of nonimmediate

reactions to B-lactam antibiotics. Allergy 2004

Stevens-Johnson Syndrome Stevens-Johnson Syndrome

• Severe skin reaction • Prodrome
• Type IV hypersensitivity disorder • 1-3 days before skin findings
• Fever
• May also involve mucous membranes
• Flu-like malaise
• Usually triggered by drugs
• Lesions start on face/chest
• Hallmark: necrosis of the epidermis
• Spread symmetrically
• Nikolsky sign
• Red, tender skin
• Skin slips off with gentle tug
• Also seen in Staph Scalded Skin (child) • Progresses to vesicles/bullae
• Also seen in Pemphigus vulgaris • Sloughing of skin
Dr. Thomas Habif/Wikipedia
• Mucosal lesions: 90% cases

32
Stevens-Johnson Syndrome Erythema multiforme
• Toxic epidermal necrolysis • Skin disorder associated with infections (90% cases)
• Severe form SJS (>30% skin) • Herpes simplex virus (most common)
• High mortality • Mycoplasma pneumoniae (often in children)
• SJS 1-5%; TEN 25-35% • Also associated with some drugs
• Sulfa drugs
• NSAIDs
• Phenytoin
• Also some cancers and autoimmune diseases

Pixabay/Public Domain

Erythema multiforme Erythema multiforme

• Pathogenesis unclear • Multiple lesion types (multiforme)
• Most data from HSV-related cases • Macules, papules, vesicles
• Lesions similar for one patient
• Cell-mediated (type IV) autoimmune
• May differ between patients
• Triggered by viral antigens in keratinocytes
• Hallmark: “Target lesion”
• Dark/dusky central area
• Surrounding red rings

Kilbad/Wikipedia

Erythema multiforme Erythema multiforme

• Symmetrical distribution • Typical case
• Starts on “extensor surfaces of acral extremities” • Oral or genital HSV eruption (or other trigger)
• Backs of hands, feet • EM skin eruption occurs few days to 2 weeks later
• Contrast with SJS: face • Lesions evolve over 3-5 days
• Resolve within 2 weeks (no treatment)
• Spreads to center (“centripetal spread”)
• Rarely severe cases require steroids or other Rx
• May involve mucous membranes
• Mouth, eye, genitals
• Erythema
• Erosions (painful)
• Bullae

James Heilman, MD /Wikipedia

33
 Skin Cancer

Skin Cancer
Jason Ryan, MD, MPH

Mikael Häggström/Wikipedia

Actinic Keratosis Actinic Keratosis

Solar keratosis Solar keratosis

• Premalignant skin lesions • Round, red/brown papules or plaques

• Caused by sun exposure • Sun exposed areas
• Growth of atypical epidermal keratinocytes • Biopsy: Hyperkeratosis, epidermal cell dysplasia
• Can lead to squamous cell carcinoma • Parakeratosis: retained nuclei in stratum corneum
• Increasing degrees of dysplasia → malignancy

Future FamDoc

GoodFreePhotos Future FamDoc

Squamous Cell Carcinoma Squamous Cell Carcinoma

• 2nd most common skin cancer • Red, scaling plaques with sharp borders
• Arises from squamous cells in epidermis • More advanced lesions: ulcerate, keratin production
• Occurs in sun-exposed areas • May crust or bleed
• Face, lip, ears, hands
• DNA damage by UV light
• Occurs in older patients
• Rare <45 years old
• Common > 75 years old
• Less than 5% metastasize to regional nodes
• Rarely metastasize beyond nodes
Public Domain

Wikipedia/Public Domain

34
Squamous Cell Carcinoma Squamous Cell Carcinoma
Risk Factors Pathology

• Sun exposure • Classic finding: keratin pearls

• Chronic immunosuppression
• Organ transplant, HIV, long term glucocorticoids
• Chronic skin inflammation
• Burns, chronic ulcers, draining sinus tracts
• Arsenic exposure
• Found in contaminated drinking water

Department of Pathology, Calicut Medical College

Keratoacanthoma Bowen’s Disease

• Variant of SCC (“squamoproliferative tumor”) • Squamous cell carcinoma in situ
• Usually benign, self-resolving • Well-demarcated, scaly patch or plaque
• “Dome-shaped” nodule with central hyperkeratosis
• Classic feature: rapid growth (weeks) → regression
• Removed surgically or followed for regression

Jmarchn /Wikipedia Klaus D. Peter, Gummersbach, Germany

Basal Cell Carcinoma Basal Cell Carcinoma

• Most common skin cancer • “Pearly” papules or nodules
• Slow growing • May have telangiectasias on surface
• Dilated blood vessels
• Rarely metastasize Public Domain

• Most found early and excised • May ulcerate with crust in center
• Occur in sun-exposed areas • Borders may be “rolled” (rounded, thickened)
• Lowest potential for recurrence or metastases
• Basal < squamous < melanoma

M. Sand et al./Wikipedia
Public Domain

35
Basal Cell Carcinoma Basal Cell Carcinoma
• Nests of “basaloid” dark cells in dermis • “Palisading nuclei”
• Cells at periphery of nests line up in parallel

Ed Uthman, MD Ed Uthman, MD

Superficial BCC Treatment SCC and BCC

• Special variant of BCC (~30% of BCCs) • Surgical excision
• Light red to pink plaque • Cryotherapy
• Slight scale • Electrosurgery
• Most commonly occur on the trunk • Radiation therapy
• Topical chemotherapy
• High risk lesions excised
• Larger lesions
• Recurrent lesions
• Lesions in specific locations
• Immunosuppressed patients (SCC)

Public Domain

Melanoma Melanoma
Types
Nodular
• Highly malignant form of skin cancer • Superficial spreading
• ABCDE • Most common subtype
• Asymmetrical • 75% of melanomas
• Irregular border • Nodular
• Color variation • 15 to 30% of melanomas
• Diameter > 6mm • Aggressive subtype
• Evolving over time • Grow vertically 0x6adb015/Wikipedia
• 50% melanoma deaths

Wikipedia/Public Domain

36
Melanoma Melanoma
Types Types

• Lentigo maligna • Acral lentiginous

• Lentigo = small, flat, dark spot (large freckle) • Least common type (<5%)
• Confined to epidermis • Palms, bottom of foot, under nails
• Lentigo maligna = growing dark spot confined to epidermis
• Sometimes called “melanoma in situ”
• Lentigo maligna melanoma = invasion of dermis
• Slow growing → years to develops
• Spreads, darkens, becomes lumpy Lentigo maligna
• Occurs in elderly

Public Domain

Melanoma Melanoma
Risk Factors Diagnosis

• Sun exposure • Biopsy

• Especially severe sunburns in childhood • No single diagnostic feature
• Nevi Public Domain
• Nests of melanocytes
• 1/3 melanomas arise from dysplastic nevi • Atypical cells, irregular nuclear shape
• High number of nevi associate with melanoma risk • Tumor markers: S100
• Light-sensitivity of skin type • Calcium binding protein in nucleus
• Light skin pigmentation • Highly sensitive (low specificity)
• Freckles
• Poor tanning ability S100

GoodFreePhotos

Melanoma Melanoma
Treatment and Prognosis Treatment and Prognosis

• Tumor cells initially grow radially • Treatment: excision with wide margins
• Spread along epidermis and upper dermis • Metastasis
• Eventually tumor shifts to vertical growth phase • Hematogenous and lymphatic
• Tumor cells invade downward in dermis • Lungs, liver, brain (most common causes of death)
• ↑ depth of tumor = ↑ risk of metastasis
• Breslow thickness
• Distance from granular epidermis to deepest tumor cells

Pixabay

37
Melanoma Melanoma
Genetics Genetics

• BRAF gene mutations Growth

• Common (40 – 50%) in sporadic melanomas Factor
• BRAF = proto-oncogene Tyrosine
• Triggers cell proliferation on RAS activation Kinase
• V600E mutation of BRAF gene Receptor
• 90% BRAF mutations = V600E mutation RAS
• Treatable with BRAF inhibitors
• Vemurafenib and dabrafenib
PI-3K BRAF
• Increase survival in melanoma with V600E mutation

Cell Survival Cell Proliferation

38
 Neurocutaneous Disorders
Neurocutaneous Disorders
Phakomatoses

• Genetic disorders of skin, nerves and eye

• Other structures sometimes involved (bones, kidneys)
• Structures derived from ectoderm
Neurocutaneous •
•
Neurofibromatosis
Tuberous Sclerosis

Disorders •
•
Sturge-Weber syndrome
von Hippel-Lindau disease
Jason Ryan, MD, MPH

Nyq/Wikpiedia

Neurofibromatosis Neurofibromatosis 1
NF1/von Recklinghausen disease

• Familial cancer syndrome • Mutation of NF1

• Genetic disorder • Tumor suppressor gene on chromosome 17
• Encodes for neurofibromin (tumor suppressor protein)
• Autosomal dominant
• Restricts RAS function
• Mutations in NF1 or NF2 genes
• Mutation → RAS overactivity → uncontrolled growth
• NF1: Most common type
• Autosomal dominant with 100% penetrance
• Nerve tumors with skin and eye findings
• All gene carriers have disease
• Children of affected individuals → 50% chance of disease
• Variable expressivity
• Some patients: mild features
• Other patients: severe features

Neurofibromatosis 1 Neurofibromatosis 1
NF1/von Recklinghausen disease NF1/von Recklinghausen disease

• Neurofibromas • Lisch nodules

• Benign tumors • Brown spots on iris
• Develop on nerves
• Often cutaneous nerves

File Upload Bot/Public Domain

File Upload Bot/Public Domain

39
Neurofibromatosis 1 Neurofibromatosis 1
NF1/von Recklinghausen disease NF1/von Recklinghausen disease

• Café-au-lait spots • Optic gliomas

• “Coffee with milk” • Usually develop by 3 years of age
• Light brown macules • Bone abnormalities
• Freckles • Curvature of long bones
• Not random • Facial deformity of eye socket
• Clusters in skin folds • Scoliosis
• Axilla and groin • Intellectual impairment
Wikipedia/Public Domain

File Upload Bot/Public Domain

Neurofibromatosis 1 Neurofibromatosis 1
NF1/von Recklinghausen disease NF1/von Recklinghausen disease

• Hypertension • Diagnostic criteria

• Renal artery stenosis • Six or more café-au-lait spots
• Rarely pheochromocytoma • Two or more neurofibromas
• Malignant tumors • Freckles in axilla or groin
• Some neurofibroma become malignant • Optic glioma
• Usually not skin lesions • Two or more Lisch nodules
• Peripheral nerve sheath tumors • Bone lesions
• Occurs in adolescence or adulthood • 1st degree relative with NF1
• Presents as pain or sudden growth of neurofibroma

Neurofibromatosis 1 Neurofibromatosis 2
NF1/von Recklinghausen disease

• Birth to 2 years • Less common than NF1

• Café-au-lait spots • Also autosomal dominant
• Bone abnormalities
• Mutation of NF2 gene
• Optic gliomas
• Major features: CNS tumors
• Age 2 to 6
• Bilateral schwannomas
• Lisch nodules
• “Acoustic neuromas”
• Developmental delay
• Occur in almost all patients
• Adolescence (puberty)
• Meningiomas
• Cutaneous neurofibromas

40
Schwannoma Tuberous Sclerosis
• Schwann cells: Glial (non neurons) of PNS • Familial cancer syndrome
• Classically located to CN VIII • Hallmark: hamartomas
• Hearing loss, tinnitus, ataxia • Benign malformation of cells/tissue
• Resembles tissue of origin (skin, lung, spleen)
• Main clinical feature: seizures
• CNS hamartomas

Hellerhoff/Public Domain

Tuberous Sclerosis Tuberous Sclerosis

• Autosomal dominant with variable expressivity • Widespread tumor formation
• De novo mutations: 80% cases (no family history) • Involves MULTIPLE organ systems
• Mutation in TSC1 or TSC2 gene • Numerous hamartomas and other neoplasms
• TSC1: Hamartin
• Classic features
• TSC2: Tuberin
• Seizures – most common presenting feature
• Proteins inhibit mTOR • “Ash leaf spots”: Pale, hypopigmented skin lesions
• Mechanistic target of rapamycin • Facial skin spots (angiofibromas)
• Kinase • Intellectual impairment
• Mutation → mTOR overactivity → cell growth
• Especially cell size

CNS Tumors Tuberous Sclerosis

Subependymal giant cell astrocytomas

• Cortical tubers • Low grade astrocytoma

• Distorted cortex • Usually occur at interventricular foramen
• Seizures
• May obstruct ventricles → hydrocephalus
• Subependymal nodules
• Ependyma = lining of ventricles

Wikipedia/Public Domain
Hellerhoff/Wikipedia Hytham Nafady

41
Tuberous Sclerosis Tuberous Sclerosis
Angiofibromas Ash Leaf Spots

• Fibrous papules usually on face • Hypopigmented macules

• Usually oval or elliptical

Mohd Hanafi
Herbert L. Fred, MD and Hendrik A. van Dijk

Tuberous Sclerosis Tuberous Sclerosis

Shagreen patches Ungual fibromas

• Connective tissue hamartoma • Fibromas beneath nailbeds

• Usually found on lower back
• “Orange peel” or “leathery” texture

R. Verma/Public Domain
K. Chinnasamy

Tuberous Sclerosis Tuberous Sclerosis

Rhabdomyomas Renal Angiomyolipomas

• Tumors of muscle cells • Most frequent renal manifestation

• Benign (do not metastasize) • Multiple/bilateral
• Classic cardiac feature of TS (90% cases) • Proliferation of epithelioid cells around vessels
• Sometimes detected prenatal • Growth and hemorrhage → pain
• Tumor embedded in ventricular wall • May cause renin-dependent hypertension
• Rare symptoms from obstruction, arrhythmia • Risk of chronic kidney disease
• Compression of normal renal tissue

42
Tuberous Sclerosis Tuberous Sclerosis
Renal Angiomyolipomas Classic Case

• Child/infant
• Seizures
• Ash-leaf spots
• Angiofibromas

Hellerhoff/Wikipedia

Sturge-Weber Syndrome Sturge-Weber Syndrome

Genetics

• Congenital vascular disorder of capillaries • Spontaneous mutation in GNAQ gene

• Spontaneous gene mutation in early development • Occurs after fertilization (somatic mutation)
• Not inherited
• Mosaicism (some cells normal, some mutated)
• Three classic features • Abnormal capillary formation/growth
• Port-wine stain on face (birthmark)
• Leptomeningeal angioma (brain tumor)
• Increased ocular pressure (glaucoma)

Wikipedia/Public Domain Wikipedia/Public Domain

Sturge-Weber Syndrome Sturge-Weber Syndrome

Port-Wine Stain/Nevus Flammeus Leptomeningeal angioma

• Malformation of dermal capillaries and venules • Leptomeninges: pia mater and arachnoid
• Occurs on face in SWS • Angioma: capillary-venous malformation
• Unilateral • Occurs on same side as port-wine stain
• 1st/2nd trigeminal area • May cause seizures (80% patients)
• Slow/low blood flow • Often begin first 2 years of life
• Pink/red patches • May cause hemiparesis, headaches
• Apparent at birth
• Does not regress
• Grows as child grows Lee Health/Vimeo

43
Sturge-Weber Syndrome Sturge-Weber Syndrome
Glaucoma Classic Case

• In infancy or early adulthood • Newborn with port wine stain

• Exact mechanism unclear • Seizures
• Abnormalities anterior chamber angle • Glaucoma
• Elevated venous pressure in episclera
• Choroidal hemangiomas
• Causes vision impairment

Petr Novák, Wikipedia

von Hippel-Lindau Disease von Hippel-Lindau Disease

• Genetic cancer syndrome
• Multiple benign/malignant tumors
• von Hippel-Lindau (VHL) gene
• Chromosome 3
• Codes for VHL tumor suppressor protein
• Ubiquitination of hypoxia-inducible factor
• Post-translational modification
• Addition of ubiquitin to proteins (small protein)
• Tags proteins for destruction in proteasome
• Cells behave as if hypoxic → blood vessel growth

Simon Caulton/Wikipedia

von Hippel-Lindau Disease von Hippel-Lindau Disease

• Multiple hemangioblastomas
• Clumps of capillaries (“angiomatosis”)
• Bright red on gross examination
• Well-circumscribed, benign
• No invasion or metastasis
• Symptoms: compression of other structures, hemorrhage
• Occur in CNS
• Rarely occur sporadically outside VHL
• Classic locations: cerebellum, spinal cord, retina

Wikipedia/Public Domain

44
von Hippel-Lindau Disease von Hippel-Lindau Disease
• Renal cysts • Requires “two hits”
• Renal cell carcinomas (bilateral) • One abnormal gene inherited (germline mutation)
• Second spontaneous mutation → disease
• Pheochromocytomas
• Similar to retinoblastoma, Li-Fraumeni, FAP
• “Autosomal dominant”
• Onset usually late childhood to young adulthood
• Takes years for second hit to occur

Wikipedia /Public Domain

45