Skin Path (Gomez) Flashcards
Fibroepithelial Polyps (FEP)
Also known as skin tags acrochordon fibroma molle squamous papilloma
Occur in individuals usually age 30 or greater and particularly in obese individuals
Associated with areas of rubbing by clothing; collar of neck or groin
Has vascular supply and variable stroma from fatty to fibrous
Epithelial Inclusion & Pilar Cysts
Also known as
epidermal cyst
follicular infundibular cyst
wen
Occur in areas with lots of hair follicles (face, scalp, trunk)
Caused by obstruction of hair follicle at infundibulum
- Filled with keratinous debris
Lining of cysts - Epithelial inclusion: squamous epithelium with a granular cell layer
- Trichilemmal/pilar: squamous epithelium with no granular cell layer
Rupture (trauma) → pain and
* foreign body granulomatous giant cell inflammatory reaction to the keratinaceous debris
Seborrheic Keratosis (SK)
Proliferation of * epidermal basal cells
Usually middle-aged or older
Roundish, flat & elevated
“Postage stamp” appearance
On non-exposed skin (trunk, proximal extremities, lateral neck)
Many have mutations in fibroblast growth factor receptor 3
Removed for cosmetic reasons or untrained clinician thinks it resembles a malignant melanoma
* Sign of Leser-Trélat – acute onset of SKs with malignancies (GI mostly)
Adnexal Neoplasms
Overwhelming majority (99%) are benign Arise from the ductal and glandular epithelial cells of adnexa
Benign adnexal tumors are
Symmetrical, small (<1 cm), superficial, vertically orientated
Malignant adnexal tumors are Asymmetrical, large, deep, wide Sebaceous carcinoma Most common type of malignant adnexal neoplasm, but quite uncommon Eccrine carcinoma Apocrine carcinoma
Hundreds of different neoplasms arise from or have adnexal features!!!
(eccrine or apocrine glands or ducts, hair-bulb germinal epithelium or sebaceous glands)
Cowden syndrome
multiple tricholemmomas with dominant inheritance (hair follicles)
Muir-Torre syndrome
sebaceous adenomas with association colorectal malignancy (variant of Lynch)
Turban tumor
massive confluent cylindromas (forehead and scalp - eccrine gland)
cylindroma occurs where?
forehead
trichoepithelioma occurs where?
eyes, nose, cheek
Dermal Lumps and Bumps- colors
Hemangioma - Red
Xanthomas – Yellow
Fibrohistiocytic lesions – normal tan-brown skin tone or darker
Benign Fibrous Histiocytoma
More common name is * dermatofibroma Benign In adults, frequently on the legs of young – middle aged women Tan-brown, usually <1.0 cm May occasionally be tender
Some Benign Skin Pigment Disorders
↑ melanin in keratinocytes: Normal number melanocytes
- Suntan
- Freckles
- Café au lait spots
- Melasma
↑ melanin in keratinocytes: small ↑ melanocytes
- Solar lentigo
Acquired pigmentation
- Skin tattoo
- Amalgam tattoo
↓ melanin in keratinocytes
- Acute transient vitiligo
- Albinism
Loss of melanocytes
- Chronic vitiligo
Suntan
Due to ultraviolet light exposure
UVB exposure → ↑ melanosomes in melanocytes → ↑ melanin per keratinocyte→ ↑ protection against solar radiation (mid-UV [UVB] spectrum)
- Chronic skin damage and neoplasia also induced by exposure to ultraviolet radiation
hypermelanosis
small spots = freckles (ephelides)
large area = cafe au lait spot
Neurofibromatosis Type 1
Autosomal dominant disorder
* NF1 gene mutation that blocks encoding of neurofibromin (RAS inhibitor)
* Neurofibromas (including plexiform)
Can develop * malignant nerve sheath tumors
* Café au lait spots (macules)
Freckles in axilla
Optic nerve gliomas
* Lisch nodules on iris
(melanotic hamartomas)
Macrocephaly
ScoliosisMelasma (Chloasma)
= mask of pregnancy
Blotchy hypermelanosis
Symmetrical
Cheeks and forehead
Less frequently on upper lip and neck
Women»_space;> men
Occurs with
Pregnancy
Oral contraceptives
Menopause
Acanthosis Nigricans
- Epidermal hyperplasia of stratum spinosum and hyperpigmentation
Prefers flexural regions
axillae, skin folds of neck, groin and anogenital regions
- 80% occur with benign conditions
- Autosomal dominant forms with variable penetrance
- Onset during childhood or puberty
- Also occur with * obesity or endocrine abnormalities
- 20% are paraneoplastic
- *Malignancy (adenocarcinoma) signals the epidermis to undergo epidermal hyperplasia.
- Usually middle-aged or older individuals
Tattoo = Acquired Pigmentation
Intentional or incidental (pencil “lead” breaking in skin or oral amalgam injury)
May mimic pigmented lesions if incidental
May “bleed” if pigment travels into dermis & macrophages move
Will fade over time as pigments move deeper and out of dermis
Solar Lentigo
(Lentigo Senilis, Lentigo Simplex)
Benign, discrete hyperpigmented macule on chronically sun exposed skin
Back of hands and the forehead
Variable increase in number of junctional melanocytes
Increased melanin pigment in keratinocytes
what lentigo or lentiginous means
Note: “lentigo or lentiginous” means a proliferation of melanocytes
Lentigo maligna is the name given to an in situ melanoma arising in sun exposed skin and not related to a benign solar lentigo
Macular (or Patch) Skin Depigmentation
Loss of melanin in keratinocytes
- Acute transient vitiligo
- — e.g. keratinolytic agents that remove layers of pigmented keratinocytes
- Albinism
- — Defect in tyrosinase, an enzyme necessary for melanin production
Permanent lack or loss of melanocytes:
Chronic vitiligo
Melanocytic (Nevocellular) Nevi
Benign Neoplasms of Melanocytes
- Neoplastic nested melanocyte proliferation (clusters)
- Junctional: Basal epidermal nests (Maculopapular)
- Compound: Basal epidermal & dermal nests (Papular)
- Intradermal: Dermal nests: Papular to nodular - Acquired mutations in NRAS and BRAF are commonly found
- Mutations induce melanocyte neoplasia short of malignancy
Postulated Natural History of Nevi
Stage:
I- Junctional (nests of melanocytes along base of the epidermis)
II- Compound (nests of melanocytes at base of the epidermis and in the dermis)
III- Intradermal = Dermal (nests of melanocytes present only in the dermis)
IV- Neurotized (melanocytes change appearance from epithelioid to spindled shape)
Congenital Nevus
Present at birth (birthmark)
Benign, but melanoma can arise in the larger congenital nevi
Extensive deep dermal to subcutaneous growth with proliferative nodules
Blue Nevus
Intradermal, roughly wedge-shaped and slightly raised skin surface
Thin, delicate * melanocytes in a dense reactive fibrotic stroma
Melanin pigment in melanocytes, melanophages, or other adjacent structures cause the bluish color
Benign with no significant risk for development of melanoma
Spitz Nevus= Spindle & Epithelioid Cell Nevus
Usually in children and young adults
red or brown
can mimic a melanoma (clinically and histologically)
Characteristic raining down melanocyte pattern and Kamino bodies (eosinophilic amorphous globules)
Halo Nevus
- Involuting (regressing) nevus with extensive * lymphocyte infiltration and depigmentation of surrounding skin
Dysplastic (Clark) Nevus
Gross appearance is worrisome for melanoma
Asymmetric
Border irregular
Color uneven
Diameter > 6 mm
Occur on non-sun or sun exposed skin
Melanocyte nests at the tips of rete ridges
* Rete ridges are often “bridged” (connected at their bases)
* Reactive fibrosis of papillary dermis
Two forms Sporadic: not prone to malignancy Familial dysplastic nevus syndrome - Autosomal dominant - * 50% chance of melanoma by age 60
Malignant Melanoma
Subtypes
- Lentigo maligna (in situ sun exposed area)
- Lentigo maligna melanoma (invasive lesion similar to lentigo maligna)
- Superficial spreading (invasive, mostly horizontal growth phase)
- Nodular (invasive, mostly vertical growth phase)
- Acral lentiginous (palms, soles and subungual; non-caucasian; in situ or invasive)
May occur in any skin location and occasionally in the eye, mucous membranes of the genitalia, anus, oral cavity, or other sites
Most melanomas occur in sun damaged skin (also occur in non-sun exposed skin)
- Occurs * primarily in adults; beginning in 3rd decade
- * 90% originates de novo (isolated non-syndromic lesion)
Can arise in or adjacent to a pre-existing melanocytic nevus
- * Aggressive malignancy that metastasizes widely with significant mortality*
— Metastasizes to regional lymph nodes, liver, lungs, and brain
Malignant Melanoma: Risk Factors & Mutations
Caucasians with * fair skin
- Albinism or genetic syndrome such as xeroderma pigmentosa dramatically increases incidence (50X-100X)
Prolonged MCB * UV exposure
- 3 episodes of “peeling” or severe
sunburn before age 20 - Male gender
Increased telomerase activity from mutated * TERT gene is present in 70% of skin melanomas but not routinely clinically tested
10% to 15% of melanomas are familial
BRAF and NRAS mutations are also present in benign melanocytic nevi and are not sufficient for malignant transformation
Mutations seen in both dysplastic nevus and melanoma familial syndromes
Proliferation: P16 inhibition is inhibited by CDKN2A mutations; CDK4 mutations block p16 inhibition
The ABCD Checklist for Melanoma
A = Asymmetry
Melanoma if lesion bisected & halves not identical
B = Border irregularity
Melanoma if the border
is uneven or ragged
C = Color variation
Melanoma if more
than one shade of pigment
D = Diameter- Melanoma if diameter
greater than 6 mm
Malignant Melanoma stats
Best prognostic indicator on skin biopsy is Breslow level (thickness from epidermal granular layer to deepest dermal penetration)
10 year survival: 92% for melanoma < 1.00 mm thick; 80% if 1.01 to 2.00 mm
Melanoma survival depends on stage: Melanoma metastatic to lymph node(s) represents regional disease (II/III); any distant metastasis is stage IV.
Chronic Actinic Skin Damage types
solar elastosis
solar lentigo
actinic keratosis
Solar elastosis
Permanent, incremental damage to reticular collagen (elastosis)
Loss of normal skin texture (leathery and wrinkled)
Solar lentigo
Focal autonomous overproduction of melanosomes +/- mild melanocyte hyperplasia
Actinic keratosis
Neoplastic precancerous proliferation of keratinocytes
- Does not involve full epidermal thickness
- Size of lesions varies
Erythematous, reddish-brown macules or minimally elevated papules
- Increased keratin production (scaling)
- Dermal increase in vascularity (redness)
Middle-aged and elderly individuals
- Face (particularly forehead), neck , dorsum of arms and hands, lips (actinic cheilitis)
Usually asymptomatic, may have mild tenderness
other names for actinic keratosis
Solar Keratosis, Senile Keratosis & Keratinocytic Intraepidermal Neoplasia
Squamous Cell Carcinoma (SCC)
Malignant neoplasm of the basal regenerative epithelium of the epidermis
- Malignant keratinocytes resemble maturing squamous cells
- The malignant keratinocytes penetrate past the dermal-epidermal junction basement membrane (potential for metastasis)
- Exception: SCC in situ (e.g. Bowen disease, penile erythroplasia of Queyrat)
- Epidemiology:
Second most common cutaneous malignancy (#1 is basal cell carcinoma)
Incidence increases with increasing age
M>F - Primary etiology in sun exposed skin
- Long term sun exposure
Immunosuppression increases incidence of invasive SCC
- Long term sun exposure
- SCC of skin occurs in 40-70% in organ transplant recipient patients
- Increased incidence with HIV
Squamous Cell Carcinoma- Other etiologic agents (can be synergistic with sunlight)
* Human papillomavirus (HPV) Chronic skin inflammation, ulcers and draining * fistulous tracts (osteomyelitis) Some dermatoses Burns Ionizing radiation Chemical exposures - Tars → * scrotal cancer in chimney sweeps - Arsenic ingestion - Tobacco and betel nut usage
Genetic syndromes
- Epidermodysplasia verruciformis (predisposition to HPV infections and HPV subtypes 5 and 8 can lead to SCC)
- Xeroderma pigmentosa (nucleotide excision repair pathway defects)
- Other syndromes
Squamous Cell Carcinoma: Major Clinical Characteristics
Areas of greatest cumulative sun exposure
Early invasive SCC is usually a small, firm, skin-colored or erythematous nodule with indistinct margins
Surface may be smooth, verrucous, ulcerated, papillomatous or granular and may bleed easily
Older SCCs are larger, invasive, and may be ulcerated
Mortality is low for SCC of skin
Keratoacanthoma
Better term * “Squamous cell carcinoma, Keratoacanthoma type”
Variant of invasive SCC
Occurs on sun-exposed area
M>F
- Rapidly growing (days-weeks)
- Often involutes and clears spontaneously within 3 to 4 months
Basal Cell Carcinoma
Previously known as “basal cell epithelioma”
Malignant neoplasm of the basal regenerative epithelium of the epidermis
Malignant keratinocytes resemble squamous cells of the basalis layer
Almost never metastasizes
Numerous subtypes
- Nodular and sclerosing types
- Have local invasion and destruction of adjacent dermis
- Tend to occur in hair-bearing skin subjected to sun exposure
- Sclerosing and multifocal superficial spreading types
- Have difficult to identify margins
- Have high incidence of post resection recurrences
Etiology
Increased sunlight exposure in childhood and adolescence, and chronic exposure during adulthood
Nevoid Basal Cell Carcinoma Syndrome
(Gorlin Syndrome)
Multiple basal cell carcinomas before age 20 Pits of the palms and soles Odontogenic keratocysts Medulloblastomas Ovarian fibromas
- Autosomal dominant disorder with * PATCH1 * gene mutations
- SMO is normally inactive via PATCH1 function
- When hh (sonic, Indian and Desert) proteins bind to PATCH1, SMO is activated leading to production of transcription factors (GLI1) that drive gene activation
- PATCH1 mutations in Gorlin syndrome bypass the hh protein needed for SMO activation and SMO is active in the absence of hh proteins
Basal Cell Carcinoma epidemiology and major clinical characteristics
85% occur on head and neck
Remainder predominantly on trunk/limbs
* Clinical appearance related to histologic type
** Rodent Ulcer = advanced presentation
Most common cutaneous neoplasm (but is ignored in cancer data statistics)
98% occur after age 40
After age 50, 1% of population develops BCC each year
M ~ F
Almost all individuals with a significant history of face/neck sun exposure will develop one or more BCCs
Nodular BCC
Traditional or “classic” appearance of BCC
Dome-shaped, * pearly papule or nodule
Prominent surface * dilated dermal vessels (telangiectasia)
May become quite large if neglected
Easily treated by excision
Sclerosing (Morpheaform) BCC
Typically waxy yellowish-white or pearly white, indurated plaque that may retract below plane of skin surface
Occurs predominately on face
Poorly defined margins (edge of lesion)
- Difficult to excise, high recurrence rate and may disfigure
- * Mohs surgery can be used during excision to determine complete excision
Superficial BCC
Multifocal erythematous, scaly plaque; elevated rolled edges
Occurs on * non-sun exposed skin sites on proximal limbs or trunk
Multifocal growth pattern localized to dermal-epidermal junction
- Part of a “field defect” and therefore can recur after excision
Do not become locally invasive or metastasize
If pigmented may be confused clinically with melanoma
Dermatofibrosarcoma Protuberans
Malignant * superficial fibroblastic neoplasm (fibrosarcoma of skin)
Locally aggressive but rarely metastasizes
* Bednar tumor is pigmented variant
Mycosis Fungoides
Mycosis Fungoides
CD4+ T-cell lymphoma of the skin (CLA, CCR4 & CCR10)
Aggressive neoplasm with median survival 8-9 years (M>F)
Phases
- * Inflammatory erythrodermic pre-mycotic patch
- * Plaque
- * Tumor
- Sezary syndrome is variant in which skin involvement is manifest as a * generalized exfoliative erythroderma
Leukemic phase with * Sezary cell (cerebriform nuclei) seen in Sezary syndrome and 25% of plaque and tumor phases with survival <3 years
Mastocytosis/Mastocytoma
Darier sign – stroking of the skin leads to histamine release which causes swelling, erythema and edema
Mast cell granules can be highlighted with toluidine blue or Wright-Giemsa stains
