Benign epithelial neoplasms are common and probably arise from stem cells residing in the epidermis and hair follicles. These tumors grow to a limited size and generally do not undergo malignant transformation.
These common pigmented epidermal tumors occur most frequently in middle-age or older individuals. They arise spontaneously and are particularly numerous on the trunk, although the extremities, head, and neck also may be sites of involvement.
Fig. 24.13 Dermatitisherpetiformis.(A)CharacteristicselectivedepositionofIgAautoantibodyatthetipsofthedermalpapillae.(B)Lesionsconsistofintactanderoded(usuallyscratched)erythematousblisters,oftengrouped(seenhereonelbowsandarms).(C)Blistersassociatedwithbasalcelllayerinjury,initiallycausedbyaccumulationofneutrophils(microabscesses)atthetipsofthedermalpapillae.(A, Courtesy of Dr.Victor G. Prieto, Houston,Texas.)
Seborrheic keratoses are caused by acquired activating mutations in growth factor signaling pathways. A significant fraction of these tumors harbor activating mutations in fibroblast growth factor receptor 3 (FGFR3), which possesses a tyrosine kinase activity that stimulates RAS and the PI3K/AKT pathway, while others have activating mutations in downstream pathway components such as RAS and PI3K. Except for cosmetic concerns, seborrheic keratoses are usually of little clinical importance. However, in rare patients hundreds of lesions may appear suddenly as a paraneoplastic syndrome (sign of Leser-Trelat). Patients with this presentation may harbor internal malignancies, most commonly gastrointestinal tract carcinomas, which produce growth factors that stimulate epidermal proliferation.
MORPHOLOGYSeborrheickeratosesareround, exophytic, coinlike plaques thatvaryindiameterfrommillimeterstocentimetersandhavea“stuck-on” appearance(
Fig.24.14 ,inset).Theyaretantodarkbrownandhaveavelvety-togranular-appearingsurface.Occasionally,theirdarkcolorissuggestiveofmelanoma,leadingtosurgicalremoval.
Microscopically,seborrheickeratosesarecomposedofmonotonoussheetsofsmallcellsthatresemblethebasalcellsofthenormalepidermis(see
Fig.24.14 ).Variablemelaninpigmentationispresentwithinthesebasaloidcells,accountingforthebrowncolorationseengrossly.Hyperkeratosisoccursatthesurface,andthepresenceofsmallkeratin-filledcysts(horncysts)anddowngrowthofkeratinintothemaintumormass(pseudo–horncysts)arecharacteristicfeatures.
Actinic keratosis is a premalignant lesion caused by UV-induced DNA damage that is associated with mutations in TP53 and other genes that also are frequently mutated in squamous cell carcinoma of the skin. Because such lesions usually are the result of chronic exposure to
Fig. 24.14 Seborrheickeratosis.Acharacteristicroughened,brown,waxylesionthatappearstobe“stuckon”theskin(inset). Microscopicexaminationshowsanorderlyproliferationofuniform,basaloidkeratinocytesthattendtoformkeratinmicrocysts(horncysts).
sunlight and are associated with hyperkeratosis, they are called actinic (sun-related) keratoses. The rate of progression to squamous cell carcinoma is small, varying from 0.1% to 2.6% per year. Most regress or remain stable.
MORPHOLOGYActinickeratosesusuallyarelessthan1cmindiameter,tan-brownorred,andrough(sandpaper-like)tothetouch (Fig.