Cylindromas are benign neoplasms of the skin that originate from skin appendage structures. Sporadic cylindromas are usually small, solitary tumors with few complications. Familial cylindromatosis is a rare, autosomal dominant genetic predisposition to the development of multiple cylindromas. This can be a severely disfiguring condition associated with considerable morbidity.
There is a single familial cylindromatosis susceptibility gene (CYLD) located on chromosome 16q12. Loss of heterozygosity on chromosome 16q in both familial and sporadic cylindromas indicates that CYLD is a tumor-suppressor gene/recessive oncogene. Germ line mutations of CYLD are found in cylindromatosis families and somatic mutations in sporadic and familial cylindromas. However, no somatic mutations have been found in other types of neoplasm. All currently identified mutations are predicted to cause truncation or absence of the encoded protein.
CYLD encodes a 956-amino acid protein. It includes three Cytoskeletal-Associated Protein-Glycine conserved (CAP-GLY) domains that are found in proteins coordinating the attachment of organelles to microtubules. It also has sequence homology to the catalytic domain of ubiquitin C-terminal hydrolases, a family of enzymes that act to deubiquitinate proteins. However, the critical biological activities that are subverted by the CYLD mutations that result in cylindromatosis have yet to be elucidated.
Cylindromas are neoplasms derived from skin appendage structures. To inform understanding of the pathogenesis and phenotype of these tumors, we review briefly the anatomy and function of appendageal skin structures. The skin is composed of the epidermis, the dermis, and a set of epidermal appendageal structures that serve a wide range of functions. The latter include hair follicles, eccrine glands, apocrine glands, and sebaceous glands. Figure 61–1 shows a representation of the skin appendages and their anatomic interrelationship. During development, the progenitors of skin appendages are believed to originate from the embryologic basal cell layer (stratum germinativum) of the epidermis.
Representation of the skin and its appendageal (adnexal) structures.
Hair follicles are found in most areas of the skin, excluding the palms of the hands and soles of the feet, and are present at highest density in the scalp and pubic regions. Most of the five million hair follicles that are present in adult humans are formed by the fifth month of gestation, and new follicles probably do not form after birth. Sebaceous glands are closely associated with hair follicles and are similarly distributed on all skin surfaces with the exception of the palms and soles. They secrete sebum, an oily substance that functions as a lubricant, prevents excess evaporation from the skin surface, and protects the hair from becoming brittle. After birth, sebaceous glands are relatively inactive, but are activated by the increased circulating concentration of sex hormones at puberty. Eccrine glands are also widely distributed over the skin except for a few areas such as the margins of the lips, nail beds of the ...