Cellular and Immunological Aspects of Basel Cell Carcinoma

The skin, which is the largest organ of the human body, has several important functions such as protection against infections and chemical and physical influences, regulation of temperature and water balance, vitamin D synthesis, etc. The skin consists of two layers, the dermis and the epidermis. The dennis contains fibroblasts, mast cells, macrophages and lymphocytes, blood and lymph vessels and skin adnexa such as hair follicles with sebaceous glands and arrector pili muscles, and sweat glands. The epidermis comprises four cell types: keratinocytes, melanocytes, Langerhans cells (LC) and Merkel cells. Keratinocytes are the major cell type and they play an important role in the protection against the external environment. They differentiate from the stratum basale towards the surface of the epidermis through the stratum spinosum, the stratum granulosum and finally the stratum corneum. Melanocytes are located in the stratum bas ale and their main function is the production of melanin. They also play a role in the detoxification of highly reactive molecules resulting from exposure to sunlight and other sources of UV irradiation (UVR). Epidermal LC are dendritic cells, which playa role in the skin immunology by presentation of antigens to T cells. Merkel cells represent neuroendocrine cells in the epidennis and hair follicles. Tumors from all these different cell types may develop as a result of mutations, either "spontaneously" or as a consequence of exposure to chemical, physical or viral carcinogens. Examples of physical carcinogens are X-rays, radioactivity and UVR. These carcinogens cause direct DNA damage, leading to mutations, chromosomal breaks and abnormal rearrangements [1]. Skin cancer, i.e. the sum of all malignant tumors of the epidermis and the dermis, can be regarded as a progressive "silent epidemic" of the present century. In 1990, it comprised one third of all cancers in the United States [2] and its incidence is still increasing throughout the world [3-8]. Therefore, considerable effort is being made worldwide to elucidate the etiology and pathophysiology and to improve clinical management of skin cancer. The most important and most common tumors of the skin are divided into malignant melanoma (MM), derived from melanocytes, and non-melanoma skin cancer (NMSC), of which the keratinocyte-derived tumors are far the most common ones. NMSC include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), and a smaller group consisting of premalignant lesions such as Bowen's disease and keratosis actinica. Of all skin cancers, the majority (±77%) is BCC, ±20% is SCC and the remainders are MM and a small group of rare tumors, such as fibro-epithelial tumors (Pinkus).