CYLD cutaneous syndrome
CYLD cutaneous syndrome | |
---|---|
Other names | Multiple familial trichoepithelioma, Brooke–Spiegler syndrome, familial cylindromatosis, epithelioma adenoides cysticum |
Specialty | Dermatology, surgery, oncology |
Symptoms | Multiple benign skin tumors |
Complications | Malignant tumor formation |
Usual onset | At puberty or earlier |
Duration | Lifetime |
Causes | CYLD gene mutations |
Treatment | Surgical |
Frequency | Rare |
Deaths | Rare |
CYLD cutaneous syndrome (CCS) encompasses three rare inherited cutaneous adnexal tumor syndromes: multiple familial trichoepithelioma (MFT1) (also termed epithelioma adenoides cysticum and epithelioma adenoides cysticum of Brooke
Individuals with the MFT1, BSS, and FC forms of CCS carry a
Individuals with CCS generally develop increasing numbers of benign skin tumors beginning in their youth and continuing throughout most of their lives. In uncommon cases, they develop malignant tumors many of which appear to arise from their benign tumors. Tumors that are unacceptably symptomatic, highly disfiguring, or malignant are treated by surgical excision methods plus, in cases of malignancy or other medial considerations, radiation therapy. Radiation therapy alone may be used in cases of surgically inaccessible tumors. All individuals with CCS should have routine yearly or more frequent follow-up examinations to check for the development of malignant tumors. Individuals with CCS along with their close family members should be offered access to in depth
Presentation
Individuals with CCS generally have a family history of this disease and present with multiple (sometimes more than 100)
The MFT1 form of CCS typically presents with multiple trichoepithelioma-like tumors, the BSS form presents with cylindroma-, spiradenoma-, and/or trichoepithelioma-like tumors or papules, and the FC form typically presents with multiple cylindroma-like papules.[4] Uncommonly, individuals with CCS develop malignant tumors[9] that occur within or near to their benign tumors; they are primarily malignant counterparts to the cylindromas, spiradenomas, trichoepitheliomas and are termed cylindrocarcinomas, spiradenocarcinomas,[10] and trichoblastic carcinomas,[11][12] respectively. Some of these tumors resemble basal-cell carcinomas[13][14] or adenocarcinomas.[8] These malignant tumors may metastasize to non-cutaneous tissues such as the salivary glands (i.e.basal cell adenocarcinomas of a salivary gland[6]), liver, lungs, and/or bones.[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.[15]
Non-familial cylindromas,[16] spiradenomas,[7][13][17] spiradenocylindromas[7] and their malignant counterparts[7] present as a single isolated tumor or, less commonly, multiple tumors. These tumors are sporadic (i.e. not inherited) and may or may not consist of cells bearing a CYLD gene mutation. If present, the mutated CYLD gene's location is restricted to the tumor cells. These sporadic tumors are neither manifestations of nor diagnosed as CCS.[10]
Histopathology
As determined by the microscopic
Genetics
CCS is an
Recent studies of 14 individuals with CCS indicate that their tumor cells have lost expression of both CYLD genes. This double gene mutation in CCS tumor cells was found in all benign and some malignant CCS tumors suggesting that it may be a consistent feature in CCS.[2][8] In this view, individuals with CCS carry an inherited, germline mutation in one CYLD gene that is widely distributed to the cells throughout the body plus am uninherited, acquired mutation in the second CYLD gene (see loss of heterozygosity) that is restricted to their CCS tumor cells. The lose of both CYLD genes in hair follicle stem cells may be required for the development of CCS tumors.[5]
CYLD gene's mechanism of action
The CYLD gene is located in
The encoded product of the CYLD gene, CYLD lysine 63 deubiquitinase protein (CYLD protein), is a
Diagnosis
The diagnosis of CCS is strongly suggested by its tumors' presentations and microscopic histopathologies and the tumor bearers' family histories of CCS.
Treatment and prognoses
CCS is an inherited, life-long, familial disease which currently is incurable.
Benign CCS tumors
The treatments for benign CCS tumors are directed at removing tumors that cause unacceptable symptoms (e.g. pain, ulceration, bleeding, disfigurement, sexual dysfunction, or occlusion of a passageway such as an
Malignant CCS tumors
Primary CCS tumors that are known or suspected to be malignant and accessible metastatic tumors are currently treated with wide local excisions often followed by adjuvant radiotherapy. Wide local excision is used in order to remove all malignant cells while adjuvant radiotherapy is used to kill any malignant cells that remain behind after surgery.[7][13][14] Malignant CCS tumors uncommonly metastasize to distant, non-cutaneous sites. Histopathologically defined low-grade tumors metastasize less often than their high-grade counterparts.[10] Since past studies on the treatment of malignant CCS tumors often included, but did not clearly distinguish between, sporadic and familial cylindrocarcinoma, spiradenocarcinoma, and trichoblastic carcinoma tumors and since malignant CCS tumors are extremely rare, there are no clear data on the percentage of malignant CCS tumors that recur, metastasize, and become lethal. Clearly, however, CCS malignant tumors can produce each of these undesirable results.[7] The best treatment regimens for CCS malignant tumors are unclear and require further study.[5]
Drug treatments for CCS tumors
Trial studies have tested the therapeutic effects of drugs that inhibit the NF-κB pathway on CCS tumors. These drugs include
See also
- Trichofolliculoma
- Spiradenoma
- spiradenocarcinoma
- List of cutaneous conditions
- List of cutaneous neoplasms associated with systemic syndromes
References
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