Cylindromas are non-cancerous (benign) tumors that develop from the skin. They most commonly occur on the head and neck and rarely become cancerous (malignant). An individual can develop one or many cylindromas; if a person develops only one, the cylindroma likely occurred by chance and typically is not inherited. They usually begin to form during mid-adulthood as a slow-growing, rubbery nodule that causes no symptoms. The development of multiple cylindromas can be hereditary and is inherited in an autosomal dominant manner; this condition is called familial cylindromatosis. Individuals with the inherited form begin to develop many, rounded nodules of various size shortly after puberty. The tumors grow very slowly and increase in number over time.
The cause of sporadic, solitary cylindromas is largely unknown; however, genetic studies of sporadic cylindromas show loss of heterozygosity at and around the CYLD locus in a substantial number of cases, suggesting that this gene also plays a role in the development of sporadic tumors.
Familial cylindromatosis is inherited in an autosomal dominant fashion, and the responsible gene, CYLD, is located on band 16q12-13. Tumors exhibit loss of heterozygosity, implicating the gene as a tumor suppressor gene. o The precise biological function of the CYLD gene is yet to be elucidated. It has 4 functional motifs: CAP-GLY domains, proline-rich domains, metal-binding fingerlike domains, and regions with homology to UCH-catalytic domains.
The CYLD gene consists of 20 exons; the first 3 are untranslated and the latter 17 are coding exons. Various mutations have been observed, such as frameshift, nonsense, or splice site mutations. Most mutations occur in 3'2/3rds of the C-terminal coding portion of the gene, in exons 9-20.