ACTINIC KERATOACANTHOMA - SPECULATIONS ON THE NATURE OF THE LESION AND THE ROLE OF CELLULAR-IMMUNITY IN ITS EVOLUTION

The implications of cytologic atypia, patterns of growth, stromal refractoriness, and immune responses in actinic keratoacanthoma are examined here in a speculative manner with the following conclusion: keratoacanthoma is a generic designation for a spectrum of invasive, keratinocytic hyperplasias. In this context, hyerplasia may affect both genomically normal and abnormal keratinocytes. In keratoacanthoma, it does so indiscriminately. The universality of the process in which both benign and neoplastic clones are affected qualifies as immunostimulation. The affected keratinocytes, regardless of genomic characteristics, extend beyond their sustaining stroma into retinaculum and the basement membrane, as an immunologic barrier, is disrupted. Following a period in which the stroma and the immune response are refractory, one or more clones of keratinocytes are exposed to an immune response. For the adnexal contributions, the eventual encounter with the immune response is brief and short-lived. The fate of these genomically intact cells is predictable: complete regression is the inviolate pathway. For the genomically deranged populace, the results of the encounter are unpredictable and potentially manifold. The options, variably expressed, include regression, spatial progression (expansion in space), and neoplastic progression (expansion in the number and types of neoplastic clones). In some actinic keratoacanthomas, neoplastic clones are represented in either focal or extensive carcinomalike patterns from the inception of the hyperplasia. In them, a potential for neoplastic progressions is inherent. If autonomous, aggressive clones are selected in the progressions, the transition from universal hyperplasia (keratoacanthoma) to malignancy (carcinoma) is effected. In the transition, hyperplastic, genomically intact, follicular keratinocytes are not affected; actinically deranged keratinocytes are. The final pathway for an individual evolving lesion is unpredictable, but in some cases it leads to biologic carcinoma (carcinoma ex-keratoacanthoma).