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Genetics of Skin Cancer (PDQ®): Genetics - Health Professional Information [NCI] - Introduction

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The true cytologic origin of BCC remains in question. BCC and basal cell keratinocytes share many histologic similarities, as is reflected in the name. Alternatively, the outer root sheath cells of the hair follicle have also been proposed as the cell of origin for BCC.[2] This is suggested by the fact that BCCs occur predominantly on hair-bearing skin. BCCs rarely metastasize but can invade tissue locally or regionally, sometimes following along nerves. A tendency for superficial necrosis has resulted in the name "rodent ulcer."[3]

SCC is derived from a more differentiated keratinocyte. A variety of tissues, such as lung and uterine cervix, can give rise to SCC, and this cancer has somewhat differing behavior depending on its source. Even in cancer derived from the skin, SCC from different anatomic locations can have moderately differing aggressiveness; for example, SCC from glabrous (smooth, hairless) skin has a lower metastatic rate than SCC arising from the vermillion border of the lip or from scars.[3]

Additionally, in the epidermal compartment, melanocytes distribute singly along the basement membrane and can transform into melanoma. Melanocytes are derived from neural crest cells and migrate to the epidermal compartment near the eighth week of gestational age. Langerhans cells, or dendritic cells, are a third cell type in the epidermis and have a primary function of antigen presentation. These cells reside in the skin for an extended time and respond to different stimuli, such as ultraviolet radiation or topical steroids, which cause them to migrate out of the skin.[4]

The dermis is largely composed of an extracellular matrix. Prominent cell types in this compartment are fibroblasts, endothelial cells, and transient immune system cells. When transformed, fibroblasts form fibrosarcomas and endothelial cells form angiosarcomas, Kaposi sarcoma, and other vascular tumors. There are a number of immune cell types that move in and out of the skin to blood vessels and lymphatics; these include mast cells, lymphocytes, mononuclear cells, histiocytes, and granulocytes. These cells can increase in number in inflammatory diseases and can form tumors within the skin. For example, urticaria pigmentosa is a condition that arises from mast cells and is occasionally associated with mast cell leukemia; cutaneous T-cell lymphoma is often confined to the skin throughout its course. Overall, 10% of leukemias and lymphomas have prominent expression in the skin.[5]

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