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SKIN PATHOLOGY
EDITED BY
Dr. JUSUF FANTONI SpPA,MScPath (Glasg)
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Epidemiology
Most common human cancer
600,000 to 800,000 cases per year in U.S.
Male:Female 2-3:1
80% arise in head and neck
SCCa over 60 years old
BCCa over 40 years old
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Etiology
Ultraviolet radiation
ethnicity
ionizing radiation exposure
chemical exposure - arsenic
burns, scarring
immunosuppression
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Syndromes
Xeroderma pigmentosum
nevoid basal cell syndrome
albinism
epidermodysplastic verrucoformis
epidermolysis bullosa dystrophica
dyskeratosis congenital
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Skin
Largest organ
major functions
protection
sensation
thermoregulation
metabolic
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Skin structure
Epidermis
dermis
hypodermis
epidermal appendages
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Skin Histology
Stratum corneum
stratum lucidum
stratum granulosum
stratum spinosum stratum basale
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VITILIGO
Vitiligo is a common disorder characterized by partial
or complete loss of pigment producing melanocytes within
the epidermis.All ages and races are affected, but lesions are most
noticeable in darkly pigmented individuals.
Clinical lesions are asymptomatic, flat, well-
demarcated macules and patches of pigment loss; their
size varies from few to many cnetimeters. Vitiligo ofteninvolves the hands and wrists, axillae and perioral;
periorbital and anogenital skin
DISORDERS OF PIGMENTATION and MELANOCYTES
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Melanocytic Nevus ( Pigmented Nevus, Mole )Most of us have at least a few moles. Clinically, common
acquired melanocytic nevi are tan to brown, uniformly pigmented,
small ( usally < 6 mm across), flat (macules) to elevated ( papules )
with well-defined rounded borders.
Morphology.
Melanocytic nevi are initially formed by melanocytes that have
been transformed from highly dendritic single cells normally
intersperesed among basal keratinocytes to round cells that grow inaggregates, or nests. along the dermoepidermal junction. Nuclei of
nevus cells are uniform and rounded in contour, contain inconspicuous
nucleoli, and show little or no mitotic activity. Such lesions are believed
to represent an early developmental stage in melanocytic nevi and are
called Junc t ional nev i.
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Eventually, most junctional nevi grow into the underlying dermisas nests or cords of cells ( Compound nev i ); in older lesions, the
epidermal nests may be lost entirely to form pure Intradermal nevi.
Clinically, compound and dermal nevi are often more elevated than
junctional nevi.
Progressive growth of nevus cells from the dermoepidermal
junction into the underlying dermis is accompanied by a process
termed maturation. Less mature, more superficial nevus cells are
larger, tend to produce melanin, and grow in nests; more mature,
deeper nevus cells are smaller, produce little or no pigment and grow
in cords. The most mature nevus cells may be found at the deepest
extent of lesions where they often acquire fusiform contours and grow
in fascicl;es resembling neural tissue.
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Clinical Features.Malignant melanoma of the skin is ususally asymptomatic,
although itching may be an early manifestation. The majority of
lesions are greater than 10 mm. The most important clinical sign ofthe disease is change in color, size, or shape in a pigmented
lesion.
On occasion, zones of white or flesh-colored hypopigmentation are
also present. The clinical warning signs of melanoma are : (1)
enalrgement of a pre-existing mole, (2) itching or pain, (3)
development of a new pigmented lesion during adult life, (4)
irregularity of the borders, (5) variegation of color within a pigmented
lesion.
Growth Patterns and Morphology
Simply stated, radial growth indicates the tnedency of amelanoma to grow horizontally within the epidermal and superficial
dermal layers, often for a prolonged time. During this stage of
growth, melanoma cells do not have the capacity to metastasize., i.e.
Lentigo maligna, superficial spreading and acral / mucosal lentiginous.
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Individual melanoma cells are usually larger than nevuscells. They contain large nuclei with irregular contours and prominent
nucleoli. These cells proliferate as poorly formed nests or as
individual cells at all levels of the epidermisThe nature and extent of the vertical growth phase
determine the biologic behaviour of malignant melanoma.
Benign Epithelial Tumors
Seborrheic Keratosis
Occur frequently in middle-aged or older
individuals. They arise spontaneously and may become
numerous on the trunk; also the extremities, head, and neck
may also be involved.
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They appear as round, flat, coinlike, waxy plaques thatvary in diameter from mm to several cms. They are
uniformly tan to dark brown and show a velvety to granular
surface.
Morphology
Exophytic and demarcated sharply from the adjacent
epidermis. They are composed of sheets of small cells that most
resemble basal cells of the normal epidermis. Variable melaninpigmentation is present within these basaloid cells. Exuberant
keratin production (hyperkeratosis occurs) and small keratin-filled
cysts (horn cysts ) and invaginations of keratin into the main tumor
mass ( invagination cysts ) are characteristic
features. Interestingly, when seborrheic keratoses become irritated
and inflamed, they undergo squamous differentiation and
characterized by foci of whorling squamous cells resembling
eddy currents in a stream. When sborrheic keratoses involve the
epithelium of hair follicles, they may grow in an endophytic (
downward) fashion, and show the effects of inflammation; such
lesions are termed : Inverted fol l icular keratoses
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= slow-growing tumors that rarely metastasize.
Tendency to occur at sites of chronic sun exposure and in
lightly pigmented people. B C C rises sharply with
immunsuppresion and in patients with inherited defects in
DNA repair.
Clinically, as pearly papules often containing
prominent, dilated subepidermal blood vessels (
telangiectasias ). Some contain melanin. Advanced lesionsmay ulcerate, extensive local invasion of bone or facial
sinuses may occur after many years of neglect (=rodent
ulcers )
Basal Cell Carcinoma ( B C C )
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Tumor cells resemble those in the normal basal cell
layer of the epidermis. They arise from the epidermis or follicular
epithelium and do not occur on mucosal surfaces. Two patterns
are seen :mu l t ifocal grow ths originating from the epidermis and
extending over several square cmsor more fo skin surface and
nodular lesions growing downward deeply into the dermis ascords and islands of variably basophilic cells with hyperchromatic
nuclei, embedded in a mucinous matrix, and often surrounded by
many fibroblasts and lymphocytes. The cells forming the periphery
of the tumor cell islands tend to be arranged in approximately
parallel alignment ( palisading )
The stroma shrinks away from the epithelial tumor
nests, creating clefts or separation artifacts that assist in
differentiating basal cell carcinomas from certain appendage tumors
also characterized by proliferation of basaloid cells ( e.g.
trichoepithelioma )/.
Morphology
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Actinic Keratosis
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Keratoacanthoma
Solitary or multiple
rapid growth
1 to 2.5 cm
ulcer with keratinousmaterial
spontaneous resolution
observe, 5-FU, Mohs'
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Basal Cell Carcinoma
Raised, with pearly
border
prominent vasculature
ulceration
nodular most common
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Pigmented Basal Cell
Produce brown pigment
often mistaken for
melanoma
behave similar to
nodular
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Superficial Basal Cell
Scaly patches
irregular borders
extremities, less
common in head and
neck
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Adenoid Basal Cell
Pseudo-glandular
formation
strands of epithelial
cells in lace-like
patterns
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Basal Cell Biologic Behavior
Dependent upon stroma
locally invasive
spread along resistant planes
metastasis rare - 0.0028% to 0.1%
adenoid and keratotic types more likely
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Basal Cell Biologic Behavior
Embryonic fusion planes at risk for deep
invasion
inner canthus
philtrum chin
nasolabial groove
pre-auricular
retro-auricular sulcus
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Squamous Cell Carcinoma
Sun exposure
erythematous,
ulcerated, crusting
friable
adjacent induration
actinic vs. de novo
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Squamous Cell Metastasis
Actinic lesions 3% to
5%
de novo 8%
scar or chronic
inflammation 10% to
30%
deep invasion
higher grade
perineural invasion
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Squamous Cell Histopathology
Well, moderate and poorly differentiated
generic
adenoid
bowenoid
verrucous
spindle cell or pleomorphic
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Squamous Cell Histopathology
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Adenoid Squamous Cell
Pseudoglandular
arrangement
dyskeratosis
acantholysis
periauricular
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Verrucous Squamous Cell
Rare on skin
cauliflower-like
well-differentiated
marked hyperkeratosis,parakeratosis,
acanthosis
invasion with pushing
margins
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Staging
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Treatment - Excision
Most often used by head & neck surgeons
93% to 95% cure
advantages
specimen for evaluation
control of margins (3 to 5 mm)
disadvantages
expensive time-consuming
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Treatment - Laser
Patients with medical diseases
multiple lesions
palliation
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Treatment - Mohs Surgery
96% to 99% cure
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Treatment - Radiation
Prolonged course
radiodermatitis
carcinogenesis
useful in poor surgical patients
no control of margins
recurrence in 4.4% to 9.5%
T t t Ph t d i
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Treatment - Photodynamic
Therapy
Photosensitive drug concentrated in tumor
porphyrin, argon ion dye pump laser most
common
still experimental
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Treatment - Interferon
Interferon -
low dose, intralesional
3 times a week
flu-like illness
erythema, pain
stimulation of macrophages and NK cells
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Treatment - Chemotherapy
Retinoids
cis-platin - most widely used
bleomycin
cyclophosphamide
5-fluorouracil
vinblastine
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Treatment - Regional Lymphatics
Parotidectomy for
periauricular tumors
spare uninvolved
structures
post op XRT as
indicated
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Treatment - Selection
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Recurrence
BCCa 1-39%
Nodular 1-6%
Morpheaform 12-30%
3 years
SCCa variable
recurrence rates
75% of recurrences
occur within 2 years
95% of recurrencesoccur within 5 years
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Mortality
Exact numbers not available - not consistently
reported
0.44 per 100,000 persons per year
2,000 to 3,000 deaths per year in U.S. patients 65-70 years old
widespread SCCa arising in periauricular
region
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Conclusion
Common tumors
best chance for cure is early diagnosis and
treatment
prevent new lesions with sun protection
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