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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