Squamous cell carcinoma spreads by
Ref Robbins 9/e p273 Squamous Cell Carcinoma Squamous cell carcinoma is a common tumor arising on sun- exposed sites in older people. 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 arseni- cals, and ionizing radiation. As with squamous cell carci- nomas at other sites, those in the skin may be preceded by in situ lesions. PATHOGENESIS The most common exogenous cause of cutaneous squamous cell carcinoma is UV light exposure, which causes DNA damage (Chapter 5). TP53 mutations caused by UV light- induced DNA damage are common, as are activating mutations in HRAS and loss-of-function mutations in Notch receptors, which transmit signals that regulate the orderly differentiation of normal squamous epithelia. In addition to inducing mutations, UV light (UVB in paicular) may have a transient immunosuppressive effect on skin by impairing antigen presentation by Langerhans cells. This effect may contribute to tumorigenesis by weakening immunosurveil- lance. Patients who are immunosuppressed as a result of chemotherapy or organ transplantation, or who have xeroderma pigmentosum, are at increased risk. Tumors in immunosuppressed persons, paicularly organ transplant recipients, are likely to be associated with HPV infection. TP53 mutations caused by UV light-induced DNA damage are common, as are activating mutations in HRAS. As with squamous cell carcinomas at other sites, those in the skin may be preceded by in situ lesions. MORPHOLOGY 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 (Fig. 23-16, A). Microscopically, squa- mous cell carcinoma in situ is characterized by highly atypical cells at all levels of the epidermis, with nuclear crowding and disorganization. Invasive tumors, defined by penetration of the basement membrane (Fig. 23-16, B), show variable degrees of differentiation, ranging from tumors with cells arranged in orderly lobules that exhibit extensive keratiniza- tion to neoplasms consisting of highly anaplastic cells with foci of necrosis and only aboive, single-cell keratinization (dyskeratosis). Clinical Features Invasive squamous cell carcinomas of the skin often are discovered while small and resectable. Less than 5% have metastasized to regional nodes at diagnosis. The likelihood of metastasis is related to the thickness of the lesion and degree of invasion into the subcutis. Tumors arising in the context of actinic keratoses may be locally aggressive generally metastasize only after long periods of time, while those arising in burn scars, ulcers, and non-sun-exposed skin behave less predictably. Mucosal squamous cell carci- nomas (oral, pulmonary, esophageal, etc.) generally are much more aggressive.
Hematogenous route
Lymphatic route
Direct invasion
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General anatomy