SKIN 1 Flashcards
functions of the skin
● Sensation ● Heat regulation by sweating ● Absorption ● Protection ● Excretion of some by products or sweat ● Secretion (SHAPES)
LAYER OF THE EPIDERMIS
● Stratum corneum ● Stratum lucidum ● Stratum granulosum ● Stratum spinosum ● Stratum basale
○ cornified layer
○ contains the keratin
Stratum corneum
○ firmly adherent to the basement membrane
Stratum basale
LAYERS OF THE DERMIS
● Papillary dermis
● Reticular dermis
○ layer where capillaries are located
Reticular dermis
Mostly fat, but there are also blood vessels and
lymphatics in this layer
SUBCUTANEOUS LAYER
○ Makes up most of the skin layer
○ “Glued” tightly together by cell junctions known as desmosomes and produce
abundant amounts of keratin protein
Squamous epithelial cells (keratinocytes)
Squamous epithelial cells secrete soluble molecules that regulate and augment immune response:
■ Cytokines
■ Defensins
○ Brown pigment that absorbs and protects against potentially injurious UV radiation in sunlight
Melanocytes
○ Secrete factors that augment innate immune responses, and migrate from skin to regional lymph nodes where they present their antigenic cargoes to T
lymphocytes, stimulating the adaptive immune system
● Dendritic cells
_______ produced by these T cells mediate the microscopic patterns and
clinical expressions of cutaneous inflammatory and infectious diseases
Cytokines
Merkel cell is located in the __________
epithelial basal layer
may have neuroendocrine or mechanoreceptor functions
○ Regulate the adnexal components
○ Influence the function of the innate and adaptive immune cells in the dermis
Autonomic Efferent Nerve Fibers
Adnexal structures:
sweat glands, sebaceous
glands, hair follicles
guard against deleterious
variations in body temperature
sweat glands
have protected niches
harboring epithelial stem cells capable of regenerating superficial epithelial skin structures
Hair follicles
Traumatic lesion breaking the epidermis and
causing a linear area (e.g., deep scratch), often
self-induced
EXCORIATION
● Thickened rough skin (similar to a lichen on a
rock)
● Usually, the result of repeated rubbing
LICHENIFICATION
T or F
LICHENIFICATION is yypically seen in eczematous dermatitis
T
circumscribed, flat lesions distinguished from surrounding skin by color.
MACULA, PATCH
Macule: _mm in diameter
= 5
Patch: _mm in diameter
> 5
● Separation of nail plate from nail bed
● Can be traumatic or secondary to a fungal
infection
● Common in fungal infections of the nails (tinea
unguium)
ONYCHOLYSIS
Elevated dome-shaped of flat-topped lesion
PAPULE, NODULE
Papule: __mm across
= 5
Nodule: __mm across
> 5
● Elevated, flat-topped lesion, usually >5 mm
● Psoriasis
PLAQUE
●Dry, horny, plate-like excrescences.
● Typically, dry
● Eczema
SCALE
● Fluid-filled raised lesions
VESICLE, BULLA, BLISTER
Vesicle size
= 5mm
Bullae size
> 5mm
-Thickening of the stratum corneum
-Usually seen in cases where there is constant
friction of the skin e.g., like a callous
Hyperkeratosis
If the hyperkeratotic area shows some nucleus, it
is called
parakeratosis
● Diffuse epidermal hyperplasia
● Thickening of the epidermis
Acanthosis
○ normal: 8-10 layers thick
○ acanthosis: more than 8-10
Abnormal, premature keratinization within cells
below the stratum granulosum
DYSKERATOSIS
breakdown of epidermis, so there will be a space in between the keratinocytes
Acantholysis
● Infiltration of the epidermis by inflammatory cells
● Normally the epidermis will show only lymphocytes not PMNs
EXOCYTOSIS
● Intracellular edema within the epidermis
● Like your cellular swelling, the keratinocytes can undergo spongiosis or swelling of keratinocytes
HYDROPIC SWELLING (BALLOONING)
Linear pattern of melanocyte proliferation within the epidermal basal cell layer
LENTIGINOUS
● Surface elevation caused by hyperplasia and
enlargement of contiguous dermal papillae
PAPILLOMATOSIS (Sing. PAPILLOMA)
-can be outward or downward
Keratinization with retained nuclei in the stratum
corneum. On mucous membranes parakeratosis
is normal
PARAKERATOSIS
Most common pigmented lesions of childhood in
lightly pigmented individuals common among
European, Caucasians, not so much in Filipinos
FRECKLE (EPHELIS)
Can be seen in neurofibromatosis type 1
which is similar to freckles histologically, but differ in that they are larger, arise
independently of sun exposure, and
contain aggregated melanosomes
Cafe-au-lait spots
freckles morphology
small, tan-red or light brown macules (after sun exposure)
Hyperpigmentation of freckles results from
increased amount of melanin pigment within
basal keratinocytes
● Benign localized hyperplasia of melanocytes
● May involve mucous membranes
● Linear (non-nested) melanocytic hyperplasia
restricted to the cell layer immediately above the
basement membrane that produces hyperpigmented basal cell layer.
LENTIGO
T or F
Lentigo do not darken when exposed to sunlight
T
Melanocytis nevus is a benign neoplasms caused by acquires mutations in components of the _________
RAS signaling pathway
-Tan to brown, uniformly pigmented, usually less
than 6mm
-Proliferation of melanocytes in the dermis.
MELANOCYTIC NEVUS (PIGMENTED NEVUS, MOLE)
If it activates RAS, why do nevi only rarely give
rise to melanomas?
oncogene-induced senescence.
Expression of either activated RAS or BRAF in
normal human melanocytes causes only a limited
period of proliferation that is followed by a permanent growth arrest mediated by the accumulation of
p16/INK4a
● When cells of nevi show abnormality like nuclear
enlargement, hyperchromasia
● May be the direct precursors of melanoma
(malignancy of melanocytes)
DYSPLASTIC NEVI
Flat macules with a “pebbly” surface or target-like lesions with a darker raised center and
irregular flat periphery
DYSPLASTIC NEVI
● Irregularly shaped, dark-staining nuclei
● The dermis underlying the atypical cells characteristically shows linear, or lamellar fibrosis.
Cytologic atypia
Pathogenesis of dysplastic nevi
-loss of function mutations in CDKN2A
-RAS or BRAF
activation and increased CDK4 activity
-germline mutations that increase the expression of
TERT (gene that encodes the catalytic subunit of telomerase)
POTENTIAL STEPS OF TUMOR PROGRESSION IN
DYSPLASTIC NEVI:
A. Lentiginous melanocytic hyperplasia
B. Lentiginous junctional nevus
C. Lentiginous compound nevus with abnormal
architectural and cytologic features (dysplastic
nevus)
D. Early melanoma (radial growth phase).
E. Advanced melanoma (vertical growth phase)
● Most deadly of all skin cancers because they
grow very fast and metastasize very fast
● Strongly linked to acquired mutations caused by exposure to UV radiation in sunlight
melanoma
melanoma other sites:
oropharynx, GIT, GUT,
esophagus, meninges, uvea of the eye
In melanoma, About 10-15% are inherited as
autosomal
dominant trait with variable penetrance
Melanoma: single predisposing environmental factor
ULTRAVIOLET RADIATION from sun exposure.
Mutations involved in melanoma
● Mutations that disrupt cell cycle control genes (loss of p16/INK4a)
● Mutations that activate pro-growth signalling
pathways.
○ Aberrant increase in RAS and P13K/AKT signalling- promotes cell growth
○ Activating mutations in BRAF are seen in 40-50% of melanomas.
○ Loss of PTEN tumor suppressor leading to heightened activation of
P13K/AKT pathway
● Mutations that activate telomerase.
● Striking variations in color.
● Shades of black, brown, red, dark blue and gray.
● Borders are irregular and often notched
Melanoma
○ Larger than normal melanocytes ○ Large nuclei with irregular contour ○ Clumped chromatin at the periphery of nuclear membrane ○ Prominent red (eosinophilic) nucleoli
Melanoma cells
e tumor cells that do not
produce melanin
Amelanotic melanoma.
● horizontal spread of melanomas within the
epidermis and superficial dermis
● At this stage metastasis to other sites seem
remote
RADIAL GROWTH PHASE
indolent lesion on the face of older men
Melanoma cells are just in the basal layer. We
can still cure this with surgery.
LENTIGO MALIGNA
most common type, usually in sun-exposed skin.
melanoma cells are
already spreading at the epidermis,
SUPERFICIAL SPREADING
unrelated to sun exposure.
ACRAL/MUCOSAL LENTIGINOUS
● Tumor cells invade downward into the deeper dermal layers as an expansile mass
VERTICAL GROWTH PHASE
● Often heralded by the appearance of a nodule
● Has a metastatic potential
VERTICAL GROWTH PHASE
distance of deepest
tumor cells from the superficial epidermal
granular cell layer
BRESLOW THICKNESS
Which is more problematic: radial growth or
vertical growth?
VERTICAL GROWTH
PROGNOSTIC FACTORS
● Tumor depth (most important) that implies vertical growth phase ● Number of mitoses ● Evidence of tumor regression ● Ulceration of overlying skin ● Presence and number of tumor infiltrating lymphocytes ● Gender ● Location
WARNING SIGNS OF MELANOMA
● Asymmetry ● Borders – irregular ● Color – variegated ● Diameter – increasing ● Evolution or change in appearance
T or F
Melanomas are usually asymptomatic
T
T or F
Metastatic melanoma is resistant to conventional
chemotherapy and radiotherapy
T
Benign epithelial tumors are derived from
○ Keratinizing stratified squamous epithelium
○ Hair follicles
○ Ductular epithelium of cutaneous glands
Can be a warning sign of visceral malignancies:
○ Multiple trichilemmomas in Cowden syndrome
○ Multiple sebaceous in Muir-Torre syndrome
○ Multiple seborrheic keratosis in GIT malignancies.
● Common epidermal tumors
● Middle aged or older individuals
● Arise spontaneously and particularly numerous
on the trunk
SEBORRHEIC KERATOSES
Seborrheic keratosis:
In darker complexioned people, multiple lesions on the face are termed
dermatosis papulosa nigra
sudden eruption of multiple seborrheic keratoses in the
skin, the skin is okay and then suddenly there you
see plenty of several seborrheic keratoses
Sign of Leser – Trelat
- Round, flat, coin-like, waxy plaques
- Several keratin-filled cyst
SEBORRHEIC KERATOSES
-Thickened hyperpigmented skin with a “velvet-like” texture
-In flexural areas (axillae, skin folds of the neck,
groin and anogenital regions)
ACANTHOSIS NIGRICANS
T or F
In Acanthosis nigricans, 20% of cases are associated with cancers (GIT adenocarcinomas)
T
Acanthosis nigricans is associated with germline mutations in the receptor __________
tyrosine kinase (FGFR3)
typical signs of seborrheic keratosis.
Acanthosis, hyperkeratosis and presence of horn cysts at epidermis containing keratin
commonly called skin tag
FIBROEPITHELIAL POLYPS
T or F
Majority of fibroepithelial polyps is sporadic
T
Soft, flesh-colored, bag-like tumors often attached to
the skin by a slender stalk
FIBROEPITHELIAL POLYPS
Histologic feature of fibroepithelial polyps
fibrovascular cores covered by benign
squamous epithelium
ADNEXAL TUMORS
Eccrine poroma Cylindroma Syringomas Sebaceous adenomas Pilomatricomas
● Predominantly on palms and soles where sweat
glands are numerous
● Dermal proliferation of your sweat glands
ECCRINE POROMA
● ductal differentiation
○ Usually on forehead and scalp
○ “turban tumor” because it can grow and replace skin
CYLINDROMA
pieces of jigsaw puzzle
● Eccrine differentiation
○ Multiple, small tan papules in lower eyelids
SYRINGOMAS
irregular nest of cells
What is more common, sebaceous adenoma or carcinoma?
Adenoma
Sebaceous adenoma can be associated with what syndrome
Muir – Torre syndrome
● Follicular differentiation
● Also called calcifying epithelioma of Malherbe
PILOMATRICOMAS
Pilomatricomas distinct characteristics:
Ghost cells/Shadow
cells
PREMALIGNANT AND MALIGNANT EPIDERMAL
TUMORS
Actinic keratosis
Squamous cell carcinoma
Basal cell carcinoma
- A premalignant condition in sun-damage skin,
usually of lightly pigmented individuals.
-Exposure to ionizing radiation, industrial
hydrocarbons and arsenicals
ACTINIC KERATOSIS
● Rough sandpaper like consistency
Actinic keratosis
- lesions on the lips showing so much keratin
actinic cheilitis
ACTINIC KERATOSIS:
topical administration of ________, a drug that
activates Toll-like receptors (TLRs), eradicates
up to 50% of lesions, a rate considerably higher
than the spontaneous regression rate of
approximately 5%
imiquimod
● Second most common tumor arising on sun-exposed area
-Generally deep invasive and involve the subcutis
SQUAMOUS CELL CARCINOMA
○ The most common is basal cell carcinoma.
○ The most malignant is malignant melanoma
T or F
In Squamous cell carcinoma, Tumor incidence is proportional to the degree of lifetime sun exposure
T
HPV subtypes involved in squamous cell carcinoma
5 and 8.
● Locally aggressive, slow growing, rarely
metastasizing
● Associated with mutations that activate the
Hedgehog pathway signalling
BASAL CELL CARCINOMA
Usually present as pearly papules containing
prominent dilated subepidermal blood vessels.
BASAL CELL CARCINOMA
TUMORS OF THE DERMIS
BENIGN FIBROUS HISTIOCYTOMA
DERMATOFIBROMA PROTUBERANS
● Also called dermatofibroma ○ It is made up of fibrous tissue with presence of histiocytes. ● Legs of young and middle-aged women ● Indolent behaviour ● With numerous histologic variants
BENIGN FIBROUS HISTIOCYTOMA
BENIGN FIBROUS HISTIOCYTOMA is characterized by
downward elongation of hyperpigmented rete
ridges (pseudoepitheliomatous hyperplasia)
● Well-differentiated fibrosarcoma
● Slow growing, locally aggressive, rarely
metastasize
● Protuberant nodule, often on the trunk
DERMATOFIBROMA PROTUBERANS
pattern in dermatofibroma protuberans (micro)
Storiform (cogwheels)
The molecular hallmark of dermatofibrosarcoma
protuberans is a translocation involving the genes
encoding ___________
collagen 1A1 (COL1A1) and platelet-derived growth factor-β (PDGFB)
TUMORS OF CELLULAR MIGRANTS TO THE SKIN
MYCOSIS FUNGOIDES
MASTOCYTOSIS
MYCOSIS FUNGOIDES originates from the _________
T helper cells CD4+
Histologic hallmark of mycosis fungoides
presence of Sezary-Lutner cells
● Increased number of mast cells in the skin
MASTOCYTOSIS
In mastocytosis, most of the symptoms/signs are due to the effects of
histamine, heparin and other substances from
the mast cells
presents as a pink to tan-brown nodule that may be pruritic or show blister
formation.
Solitary mastocytoma
Many cases of mastocytosis have acquired activating point mutations in the ____
-KIT
less frequently, the PDGFR-α receptor tyrosine
kinases.
DISORDERS OF EPIDERMAL MATURATION
ICHTHYOSIS
● Chronic excessive keratin build-up producing
fish-like scales
ICHTHYOSIS
● Clinical types of Ichthyosis
o Ichthyosis vulgaris
o Congenital ichthyosis erythroderma
o Lamellar ichthyosis
o X-linked ichthyosis
Primary abnormality in ichthyosis
defective desquamation, leading to retention of abnormally formed scales
caused by a deficiency of
steroid sulfatase
X-linked ichthyosis
QUEN IS PRETTY
YES
