24.15A ).Microscopically,lowerportionsoftheepidermisshowcytologic atypia, oftenassociatedwithhyperplasiaofbasalcells(see
Fig.24.15B )orwithatrophyanddiffusethinningoftheepidermalsurface.Thedermiscontainsthickened,blue-grayelasticfibers(solarelastosis),theresultofchronicsundamage.Thestratumcorneumisthickenedandshowsabnormalretentionofnuclei(parakeratosis).Uncommonly,full-thicknessepidermalatypiaisseen;suchlesionsareconsideredsquamouscellcarcinomainsitu(
Fig.24.15C
Actinic keratoses are very common in fair-skinned individuals and increase in incidence with age and sun exposure. As would be expected, there is a predilection for sun-exposed areas (face, arms, dorsum of the hands). Despite the low risk for malignant progression, actinic keratoses are often treated, either to prevent progression or for cosmetic reasons. Local eradication with cryotherapy (superficial freezing) or topical agents is effective and safe.
Seborrheic keratosis: Round,flatplaquesmadeupofproliferatingmonotonousepidermalbasalcells,whichsometimescontainmelanin.Hyperkeratosisandkeratin-filledcystsarecharacteristic.
Actinic keratosis: Presentonsun-exposedskin,theselesionsshowcytologicatypiainlowerpartsoftheepidermisandinfrequentlyprogresstocarcinomainsitu.
Althoughbothoftheselesionsareassociatedwithoncogenicmutations,malignanttransformationisexceedinglyrareinseborrheickeratosesandoccursinonlyasmallsubsetofactinickeratoses.
Squamous cell carcinoma is a common tumor that typically arises on sun-exposed sites in older adults. These tumors have a higher incidence in men than in women.
Cutaneous squamous cell carcinoma is mainly caused by UV light exposure, which leads to widespread DNA damage and extremely high mutational loads (Chapter 6). As one might imagine, patients with the rare disorder xeroderma pigmentosum, which disrupts repair of UV-induced DNA damage, are at an exceptionally high risk. TP53 mutations are common, as are activating mutations in RAS and loss-of-function mutations in Notch receptors, which transmit signals that regulate the orderly differentiation of normal squamous epithelia.
Fig. 24.15 Actinickeratosis.(A)Red,rough(sandpaper-like)lesionsowingtoexcessivescalearepresentonthecheekandnose.(B)Basalcelllayeratypia(dysplasia)withepithelialbudsassociatedwithmarkedhyperkeratosis,parakeratosis,anddermalsolarelastosis(asterisk). (C)Squamouscellcarcinomainsitulesionshowingfull-thicknessepithelialatypia.
Immunosuppression, particularly in organ transplant recipients, is associated with an increased incidence of cutaneous squamous cell carcinomas that are likely to be associated with HPV infection. Other predisposing factors include industrial carcinogens (tars and oils), chronic non-healing ulcers, old burn scars, ingestion of arsenicals, and ionizing radiation.
MORPHOLOGYSquamouscellcarcinomasinsituappearassharplydefined,red,scalingplaques;someappeartoariseinassociationwithprioractinickeratoses.Microscopically,squamouscellcarcinomainsituischaracterizedbyhighlyatypicalcellsatalllevelsoftheepidermis,withnuclearcrowdinganddisorganization.Moreadvanced,invasivesquamouscellcarcinomasarenodular,oftenscalylesionsthatmayundergoulceration(