Squamous Cell Carcinoma
Squamous cell carcinoma is a common tumor arising on sun-exposed
sites in older people. Except for lesions on the lower legs, these tumors
have a higher incidence in men than in women. In addition to sunlight,
predisposing factors include industrial carcinogens (tars and oils), chronic
ulcers, old burn scars, ingestion of arsenicals, and ionizing radiation.
Pathogenesis.
The most common exogenous cause of cutaneous squamous cell
carcinoma is UV light exposure, with subsequent unrepaired DNA
damage. Individuals who are immunosuppressed as a result of
chemotherapy or organ transplantation, or who have xeroderma
pigmentosum, are at increased risk. In addition to inducing mutations,
UV light (UVB in particular) may have a transient immunosuppressive
effect on skin by impairing antigen presentation by Langerhans cells.This
may contribute to tumorigenesis by weakening immunosurveillance.
Immunosuppressed patients, particularly organ transplant recipients, are
likely to be associated with high-risk HPV types. p53 mutations with
associated UV mutation signatures are common, as are activating
mutations in RAS. As with squamous cell carcinomas at other sites, those
in the skin may be precedeby in situ lesions.
Morphology
Squamous cell carcinoma in situ is characterized by highly atypical cells
at all levels of the epidermis, with nuclearc crowding and disorganization.
The squamous dyplasia is broad and occupies the full thickness of the
epithelium.When these cells break through the basement membrane, the
process has become invasive . lnvasive squamous cell carcinomas exhibit
variabled differentiationr. ranging from tumors formed by atypical
squamous cells arranged in orderly lobules showing large zones of
keratinization to neoplasms formed by highly anaplastic, rounded cells
with
foci
of
necrosis
and
only
abortive,
single.cell
keratinization(dyskeratosis)
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Clinical Features.
Squamous cell carcinomas in situ appear as sharply defined, red, scaling
plaques; many arise from prior actinic keratoses. More advanced,
invasive lesions are nodular, show variable scale, and may ulcerate . The
likelihood of metastasis is related to the thickness of the lesion and degree
of invasion into the subcutis Invasive souamous cell carcinomas of the
skin are often discoveied while small and resectable; less than 5%o have
metastases to regional nodes at diagnosis
Basal Cell Carcinoma
Basal cell carcinoma, the most common human cancer, is a slow-growing
tumor that rarely metastasizes. It tend to occur at sites subject to chronic
sun exposure and in lightly pigmented people. As with squamous cell
carcinoma, the incidence of basal cell carcinoma increases with
immunosuppression (though not as dramatically as that of squamous cell
carcinoma) and in individuals with inherited defects in DNA repair.
Pathogenesis
Basal cell carcinoma has been associated with dysregulation of the sonic
hedgehog, or PTCH, pathway. Inherited defects in the PTCH gene with
subsequent loss of heterozygosity in the numerous individual tumor foci
cause the familial basal cell carcinoma syndrome, Gorlin syndrome.
Thus, PTCH functions as a classic tumor suppressor
Morphology
Tumor cells resemble the normal epidermal basal cell layer from which
they are derived. Because they arise from the epidermis or sometimes
follicular epithelium, they are not encountered on mucosal surfaces. Two
common patterns are seen: either multifocal growths originating from the
epidermis (superficial type), or nodular lesions growing downward into
the dermis as cords and islands of variably basophilic cells with
hyperchromatic nuclei, embedded in a fibrotic to mucinous matrix .
Peripheral tumor cell nuclei align in the outermost layer (palisading) with
separation from the stroma, creating a cleft or separation artifact
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Clinical Features.
Clinically, these tumors present as pearly papules, often containing
prominent, dilated subepidermal blood vessels (telangiectasia) . Some
tumors contain melanin pigment and thus appear similar to melanocytic
nevi or melanomas. Advanced lesions may ulcerate, and extensive local
invasion of bone or facial sinuses may occur after many years if neglected
Melanoma
is less common but much more deadly than basal or squamous cell
carcinoma. Today, as a result of increased public awareness of the earliest
signs of skin melanomas, most melanomas arc cured surgically
Pathogenesis
As with other cutaneous malignancies,sunlight plays an important role in
the development of melanoma. The incidence is highest in sun-exposed
skin and in geographic locales such as New Zealand and Australia where
sun exposure is high and the protective mantle of melanin is sparse.
Intense intermittent exposure at an early age is particularly harmful.
Sunlight, however, does not seem to be the only predisposing factor; the
presence of preexisting nevi and hereditary predisposition also play a role.
Morphology
Individual melanoma cells are usually considerably larger than nevus
cells. They contain large nuclei with irregular contours having chromatin
characteristically clumped at the periphery of the nuclear membrane and
prominent eosinophilic nucleoli often described as "cherry red"
Malignant cells grow as poorly formed nests or individual cells at all
levels of the epidermis and as dermal expansile, balloon-like nodules
Clinical Features.
Although most of these lesionsClinically, melanoma of the skin is usually
asymptomatic, although itching may be an early manifestation.The most
important clinical sign of the disease is a change in the color or size of a
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pigmented lesion. Unlike benign nevi, melanomas exhibit striking
variations in pigmentation, appearing in shades of black, brown, red, dark
blue, and gray . The borders of melanomas are irregular and often
"notched." The main clinical warning signs of melanoma are (1)
enlargement of a preexisting mole, (2) itching or pain in a preexisting
pigmented lesion, and (5) variegation of color within a pigmented lesion.
These principles are expressed in the so-called ABCs of ,melanoma:
asymmetry, border, color, diameter, and evolution (change of an existing
nevus). It is vitally important to recognize and intervene in melanoma as
rapidly as possible. The vast majority of superficial lesions are,cured
surgically while melanomas that become metastatic
have a virtually uniformly poor prognosis, with no effective therapy in
most cases.
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