Fig.24.16A ).Suchtumorsshowvariabledegreesofdifferentiation,rangingfromtumorswithcellsarrangedinorderlylobulesthatexhibitextensivekeratinizationtoneoplasmsconsistingofhighlyanaplasticcellswithfociofnecrosisandonlyabortive,single-cellkeratinization(dyskeratosis)(
Fig.24.16B
Invasive squamous cell carcinomas of the skin often are discovered while small and resectable. Less than 1% will have metastasized to regional lymph nodes at diagnosis. The likelihood of metastasis is related to the thickness of the lesion and degree of invasion into the subcutis. Tumors arising from actinic keratoses may be locally aggressive but generally metastasize only after long periods of time, while those arising in burn scars, ulcers, and non–sun-exposed skin often behave more aggressively. Squamous cell carcinomas arising at internal sites (oropharynx, lung, esophagus, anus) are generally invasive and aggressive, possibly because (unlike in the skin) early lesions go unrecognized.
Fig. 24.16 Invasivesquamouscellcarcinoma.(A)Anodular,hyperkeratoticlesionoccurringontheear,associatedwithmetastasistoaprominentpostauricularlymphnode(arrow). (B)Tumorinvadesthedermalsofttissueasirregularprojectionsofatypicalsquamouscellsexhibitingacantholysis.
Basal cell carcinoma is a common slow-growing cancer that rarely metastasizes. It tends to occur at sites subject to chronic sun exposure and in lightly pigmented individuals.
The molecular hallmark of basal cell carcinoma is loss-offunction mutations in PTCH1, a tumor suppressor gene that negatively regulates Hedgehog signaling; hence, tumors exhibit constitutive Hedgehog pathway activation. Excessive activation of Hedgehog in turn activates a host of downstream genes implicated in cell growth and survival and other phenotypes linked to malignant transformation. In sporadic basal cell carcinoma, PTCH1 mutations bear the telltale signs of UV light–induced DNA damage. The central role of increased Hedgehog signaling in basal cell carcinoma is further emphasized by Gorlin syndrome, an autosomal dominant disorder caused by inherited defects in PTCH1 that is associated with familial basal cell carcinoma. The Hedgehog pathway is an important regulator of embryonic development, and patients with Gorlin syndrome also often manifest subtle developmental anomalies. Mutations in TP53 caused by UV light–induced damage also are common in both familial and sporadic tumors.
Basalcellcarcinomasmanifestaspearly papules,oftenwith prominent,dilatedsubepidermalbloodvessels(telangiectasia)
Fig.24.17A ).Sometumorscontainmelaninpigmentandcanhaveanappearancesimilartomelanocyticneviormelanomas.Microscopically,thetumorcellsresemblethenormalepidermalbasalcelllayerorfolliculargerminativeelements.Becausetheyarisefromeithertheepidermisorthefollicularepithelium,theyarenotencounteredonmucosalsurfaces.Twocommonpatternsareseen:multifocal superficial growths, originatingfromtheepidermis,andnodular lesions growingdownwardintothedermisascordsandislandsofvariablybasophiliccellswithhyperchromaticnuclei,embeddedinafibroticormucinousstromalmatrix(
Fig.24.17B ).Peripheraltumorcellnucleialignintheoutermostlayer(apatterntermedpalisading),whichoftenseparatesfromthestroma,creatingacharacteristiccleft(
Fig.24.17C