Basal-cell Carcinoma - Pathophysiology

Pathophysiology

Basal-cell carcinomas are differentiated toward the folliculo-sebaceous-apocrine germ, also known as the trichoblast. Thus, another name for them is trichoblastic carcinoma, which reflects the principal line of differentiation. Over exposure to sun leads to the formation of thymine dimers, a form of DNA damage. While DNA repair removes most UV-induced damage, not all crosslinks are excised. There is, therefore, cumulative DNA damage leading to mutations. Apart from the mutagenesis, over exposure to sunlight depresses the local immune system, possibly decreasing immune surveillance for new tumor cells.

Basal-cell carcinoma also develops as a result of Basal-Cell Nevus Syndrome, or Gorlin Syndrome, which is also characterized by keratocystic odontogenic tumors of the jaw, palmar or plantar (sole of the foot) pits, calcification of the falx cerebri (in the center line of the brain) and rib abnormalities. The cause of the syndrome is a mutation in the PTCH1 tumor-suppressor gene at chromosome 9q22.3, which inhibits the hedgehog signaling pathway. A mutation in the SMO gene, which is also on the hedgehog pathway, also causes basal-cell carcinoma.