These individuals have skin tumors that tend to cluster into MFT1, BSS, and/or FC types that differ form each other in their locations, organizations, and microscopic appearances.
[6] Individuals with CCS generally develop increasing numbers of benign skin tumors beginning in their youth and continuing throughout most of their lives.
All individuals with CCS should have routine yearly or more frequent follow-up examinations to check for the development of malignant tumors.
[2] Individuals with CCS generally have a family history of this disease and present with multiple (sometimes more than 100) benign hair follicle tumors most often on their head and torso.
[7] The tumors usually begin at puberty and progressively accumulate throughout adulthood[2] although they have occurred in children as young as 1 year of age.
Cylindroma-like CCS tumors appear as smooth nodular masses that are typically pink in color, may be translucent, may have superficial blood vessels, grow progressively over many years, and can reach several cm (i.e. centimeters) in size.
Trichoepithelioma-like CCS tumors appear as skin-coloured, small, papules usually located in the skin around the nose, nasolabial fold, and/or forehead.
[2] Malignant CCS tumors occur more often in older individuals and tend to be larger (i.e. ranging up to 17.5 cm in size[7]) than their benign counterparts.
[10] As determined by the microscopic histopathological appearance of their hematoxylin and eosin-stained samples, CCS tumor tissues resemble sporadic cylindromas, spiradenomas, or trichoepitheliomas.
Cylindroma-like CCS tumors are non-encapsulated nodular lesions that extend into the dermis, consist of basal cells (i.e. small, round cells similar to those seen in the lowest layer of the skin's epidermis), and are arranged in ("jigsaw-like"[10]) cylindrical patterns separated by thickened basement membranes.
[10] Trichoblastic carcinomas differ form their benign counterparts by consisting of hypercellular, fibrous, non-myxoid stroma, often resemble and may be diagnosed as basal cell carcinomas, and in high-grade tumors have extensive areas of necrosis (i.e. dead tissue); the cells in these tumors are rapidly proliferating.
[11][12] CCS is an autosomal dominant disorder inherited from a parent carrying an inactivating mutation in one of his or her two CYLD genes.
[8] Penetrance (i.e. the percentage of individuals with CCS that exhibit symptoms of the disease) has ranged from 44% to 100% (overall average, 72%) in different studies.
[2] However, these studies usually assayed blood leukocyte samples for expression of the mRNA encoded by the CYLD gene to infer its presence.
[2][19] Recent studies of 14 individuals with CCS indicate that their tumor cells have lost expression of both CYLD genes.
The lose of both CYLD genes in hair follicle stem cells may be required for the development of CCS tumors.
The loss of CYLD protein's regulation of NF-κB signaling may be a critical contributor to the development of CCS tumors.
Testing for this gene is particularly important in cases with minimal evidence of the disease (e.g. Milia, see Presentation section) and may need to test tumor rather than blood leukocyte samples in individuals with mosaic, deep intronic, or copy number variation mutations (see Genetic section).
[2][24] Methods for these removals include surgical excision, electrodessication with curettage, dermabrasion, cryotherapy, or carbon dioxide, argon, or Er:YAG laser surgery.
[5] Trial studies have tested the therapeutic effects of drugs that inhibit the NF-κB pathway on CCS tumors.