Cellular and Immunological Aspects of Basel Cell Carcinoma

textabstractThe skin, which is the largest organ of the human body, has several important functions\nsuch as protection against infections and chemical and physical influences, regulation of\ntemperature and water balance, vitamin D synthesis, etc. The skin consists of two layers,\nthe dermis and the epidermis. The dennis contains fibroblasts, mast cells, macrophages\nand lymphocytes, blood and lymph vessels and skin adnexa such as hair follicles with\nsebaceous glands and arrector pili muscles, and sweat glands. The epidermis comprises\nfour cell types: keratinocytes, melanocytes, Langerhans cells (LC) and Merkel cells.\nKeratinocytes are the major cell type and they play an important role in the protection\nagainst the external environment. They differentiate from the stratum basale towards the\nsurface of the epidermis through the stratum spinosum, the stratum granulosum and\nfinally the stratum corneum. Melanocytes are located in the stratum bas ale and their main\nfunction is the production of melanin. They also play a role in the detoxification of highly\nreactive molecules resulting from exposure to sunlight and other sources of UV irradiation\n(UVR). Epidermal LC are dendritic cells, which playa role in the skin immunology by\npresentation of antigens to T cells. Merkel cells represent neuroendocrine cells in the\nepidennis and hair follicles. Tumors from all these different cell types may develop as a\nresult of mutations, either "spontaneously" or as a consequence of exposure to chemical,\nphysical or viral carcinogens. Examples of physical carcinogens are X-rays, radioactivity\nand UVR. These carcinogens cause direct DNA damage, leading to mutations,\nchromosomal breaks and abnormal rearrangements [1].\nSkin cancer, i.e. the sum of all malignant tumors of the epidermis and the dermis, can be\nregarded as a progressive "silent epidemic" of the present century. In 1990, it comprised\none third of all cancers in the United States [2] and its incidence is still increasing\nthroughout the world [3-8]. Therefore, considerable effort is being made worldwide to\nelucidate the etiology and pathophysiology and to improve clinical management of skin\ncancer. The most important and most common tumors of the skin are divided into\nmalignant melanoma (MM), derived from melanocytes, and non-melanoma skin cancer\n(NMSC), of which the keratinocyte-derived tumors are far the most common ones. NMSC\ninclude basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), and a smaller\ngroup consisting of premalignant lesions such as Bowen's disease and keratosis actinica.\nOf all skin cancers, the majority (±77%) is BCC, ±20% is SCC and the remainders are\nMM and a small group of rare tumors, such as fibro-epithelial tumors (Pinkus).