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Cylindroma

  • Author: Noah S Scheinfeld, JD, MD, FAAD; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Feb 08, 2016
 

Background

Cylindromas are benign skin appendage tumors. They can be seen in conjunction with spiradenomas and trichoepitheliomas. Cases of spiradenocylindromas, demonstrating characteristics of both spiradenoma and cylindroma in the same tumor mass, have also been observed, suggesting similar derivation of both tumors.

They most commonly occur on the head and neck as solitary or multiple tumors. Solitary cylindromas occur sporadically and typically are not inherited. Multiple tumors are observed in an autosomal dominantly inherited manner. When nodules enlarge and coalesce on the scalp, they form the distinctive turban tumor feature.

Malignant cylindromas are very rare. Malignant transformation may develop within solitary cylindromas, or they may complicate the multiple variant (more common).

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Pathophysiology

Cylindromas are appendage tumors previously thought to be of apocrine differentiation. While phenotypic features differ between cylindromas and spiradenomas, recent studies have shown immunohistological and cytomorphological overlap, with both tumors exhibiting apocrine, eccrine, secretory, and ductal features. Therefore, the cellular origin of cylindromas remains unknown. Cylindromas are most likely a very primitive sweat gland tumor differentiating toward either the eccrine or apocrine line.

Brooke-Spiegler syndrome (BSS) has been described as an autosomal dominant disease characterized by the development of multiple skin appendage tumors such as cylindromas, trichoepitheliomas, and spiradenomas, with a variable preponderance of any of the aforementioned subsets. Other lesions reported with BSS include parotid basal cell adenomas, organoid nevi, syringomas, and basal cell carcinomas. Despite variable phenotypic expressions of a predominant tumor in BSS, the gene responsible for multiple cylindromas, CYLD, is localized to band 16q12-q13. The mechanism of genotypic similarity and phenotypic variance is not yet understood.[1, 2]

In 2006, Zhang et al[3] reported a large consanguineous Chinese family with BSS demonstrating intrafamily phenotypic variability. Upon examination, some persons only manifested discrete, small, skin-coloured growths, while the proband manifested an expansion of multiple large growths on the nose and numerous dome-shaped papules on the scalp. Biopsy showed both trichoepitheliomas and cylindromas in the affected persons. By sequence analysis, Zhang et al identified a recurrent mutation 2272C→T (R758X) of the CYLD gene in the affected familial persons that had been previously identified in other ethnic kindreds with familial cylindromatosis.

In 2007, Stegmeier et al[4] noted that the CYLD gene encodes a deubiquitinating enzyme. The enzyme removes Lys-63–linked ubiquitin chains from I-kappaB kinase signaling components. By this mechanism, the enzyme inhibits NF-kappaB pathway activation. They demonstrated that CYLD is also required for the cell's timely entry into mitosis. Consistent with a cell-cycle regulatory function, CYLD localizes to microtubules in interphase and the midbody during telophase. CYLD 's protein levels decrease as cells exit from mitosis. Stegmeier et al identified the protein kinase Plk1 as a potential target of CYLD as a regulator of mitotic entry, and they suggested this because of the physical interaction and similar loss-of-function and over-expression phenotypes.

These findings raise the possibility that, as with other genes that regulate tumorigenesis, CYLD has both tumor-suppressing (apoptosis regulation) and tumor-promoting activities (enhancer of mitotic entry). They suggested that this additional function of CYLD could provide an explanation for the benign nature of most cylindroma lesions.

Massoumi and Paus[5] and explained the manner in which CYLD interferes with tumor necrosis factor-alpha or Toll-like receptor–mediated signaling and with JNK or NF-kappaB-dependent p65/50 signaling to limit inflammation. Additionally, the manner by which CYLD interferes with activation of the proto-oncogene BCL3 and with cyclin D1 expression to limit tumorigenesis was also explained. Finally, the researchers discussed how tumor growth-promoting agents or UV light and inflammatory mediators may activate CYLD.

Researchers have noted a MYB-NFIB gene fusion, which provides a new genetic link between dermal cylindroma and adenoid cystic carcinoma.[6]

As of 2012, researchers have identified 68 unique mutations with variable penetrance and expression (which are both intrafamilial and interfamilial) in CYLD. CYLD functions as a putative tumor suppressor gene that encodes for a deubiquitinating enzyme with functions in cell proliferation and inflammation.[7]

In 2013, a major international study noted 86 CLYD mutations in BSS and multiple familial trichoepitheliomas syndrome (MFT).[8] Of the 76 tumors from 32 patients with a germline CYLD mutation, 26 were cylindromas, 12 were spiradenomas, 15 spiradenocylindromas, 7 were other tumor types, and 15 were trichoepitheliomas. Causes of mutations included frameshift mutations, nonsense mutations, missense mutations, splice-site mutations, somatic mutations, sequence alteration, and loss of heterozygosity. Sometimes the source of mutations remained unknown. The variability of somatic mutations is underlined by this study.

Down-regulation of CLYD occurred in a case of breast cancer and may be an independent genetic mutation associated with poor prognosis.[9]

In a study of 97 tumors, all spiradenomas (27) and cylindromas (30) expressed CD200, while other eccrine (hidradenomas, poromas, dermal duct tumors, and hidroacanthoma simplex) were CD200-negative. CK15 distinguished between spiradenomas and cylindromas. This shows that cylindromas and spiradenomas are follicular tumors; specifically, Sellheyer proposed that both cylindromas and spiradenomas are adnexal neoplasms that were derived from the hair follicle bulge and that therefore cylindromas and spiradenomas represent the least differentiated follicular tumors.[10]

BSS with a new nonsense germline proband mutation of CYLD (c.1783C>T pGln 595*) has been noted.[11]

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Epidemiology

Frequency

United States

Cylindromas are uncommon. The exact incidence is not known. They continue to be reported regularly at dermatology conferences, in particular when linked to BSS.[7]

International

The exact international incidence of cylindromas is not known. A case of Brooke-Spiegler syndrome that included cylindroma was reported in China in 2013.[12]

Race

No racial disparity is reported for cylindromas.

Sex

The incidence of cylindroma is more common in females than in males. Female-to-male ratios of 6:1 and 9:1 have been reported.

Age

Solitary cylindromas are lesions that affect middle-aged and elderly persons. Multiple, inherited cylindromas usually begin in early adulthood and increase in size and number throughout life.

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Contributor Information and Disclosures
Author

Noah S Scheinfeld, JD, MD, FAAD Assistant Clinical Professor, Department of Dermatology, Weil Cornell Medical College; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Assistant Attending Dermatologist, New York Presbyterian Hospital; Assistant Attending Dermatologist, Lenox Hill Hospital, North Shore-LIJ Health System; Private Practice

Noah S Scheinfeld, JD, MD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Abbvie<br/>Received income in an amount equal to or greater than $250 from: Optigenex<br/>Received salary from Optigenex for employment.

Coauthor(s)

Anusuya Mokashi, MD, MS Resident Physician, Department of Radiology, Staten Island University Hospital

Disclosure: Nothing to disclose.

Julide Tok Celebi, MD Assistant Professor of Dermatology, Columbia University, College of Physicians and Surgeons; Consulting Staff, Department of Dermatology, New York Presbyterian Medical Center

Julide Tok Celebi, MD is a member of the following medical societies: American Academy of Dermatology, American Association for Cancer Research, Society for Investigative Dermatology, Society for Melanoma Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Christen M Mowad, MD Professor, Department of Dermatology, Geisinger Medical Center

Christen M Mowad, MD is a member of the following medical societies: Alpha Omega Alpha, Noah Worcester Dermatological Society, Pennsylvania Academy of Dermatology, American Academy of Dermatology, Phi Beta Kappa

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Abby S Van Voorhees, MD Assistant Professor, Director of Psoriasis Services and Phototherapy Units, Department of Dermatology, University of Pennsylvania School of Medicine, Hospital of the University of Pennsylvania

Abby S Van Voorhees, MD is a member of the following medical societies: American Academy of Dermatology, Women's Dermatologic Society, National Psoriasis Foundation, American Medical Association, Phi Beta Kappa, Sigma Xi

Disclosure: Received honoraria from Amgen for consulting; Received honoraria from Abbott for consulting; Partner received salary from Merck for management position; Received honoraria from Abbott for speaking and teaching; Received honoraria from Amgen for review panel membership; Received honoraria from Centocor for consulting; Received honoraria from Leo for consulting; Received none from Merck for other.

Acknowledgements

Arnold R Oppenheim, MD Assistant Professor, Department of Internal Medicine, Division of Dermatology, Eastern Virginia School of Medicine

Arnold R Oppenheim, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Clinical Pathology

Disclosure: Nothing to disclose.

References
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